Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

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Variant: NM_000215.4(JAK3):c.3268G>A (p.Ala1090Thr)

CA160243

134579 (ClinVar)

Gene: JAK3

Condition: T-B+ severe combined immunodeficiency due to JAK3 deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 2bbca366-6dfe-4d9b-9a81-9d11b903db18

HGVS expressions

NM_000215.4:c.3268G>A

NM_000215.4(JAK3):c.3268G>A (p.Ala1090Thr)

NC_000019.10:g.17826850C>T

CM000681.2:g.17826850C>T

NC_000019.9:g.17937659C>T

CM000681.1:g.17937659C>T

NC_000019.8:g.17798659C>T

NG_007273.1:g.26142G>A

ENST00000526008.6:c.*1825G>A

ENST00000696967.1:n.2445G>A

ENST00000696968.1:n.501G>A

ENST00000696969.1:n.2225G>A

ENST00000458235.7:c.3268G>A

ENST00000458235.5:c.3268G>A

ENST00000527031.5:n.2279-1540G>A

ENST00000527670.5:c.3268G>A

NM_000215.3:c.3268G>A

Benign

BA1

Evidence Links 0

Expert Panel

Severe Combined Immunodeficiency Disease VCEP

Criteria Specification Information

Criteria Specification: ClinGen Severe Combined Immunodeficiency Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for JAK3 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

NM_000215.4(JAK3):c.3268G>A is a missense variant predicted to cause substitution of Alanine by Threonine at amino acid 1090 (p.Ala1090Thr). The filtering allele frequency (the lower threshold of the 95% CI of 373/75020) of the c.3268G>A variant in JAK3 is 0.004556 for African/African American chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00447) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive severe combined immunodeficiency due to JAK3 deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: BA1 (VCEP specifications version 1).

BA1

The filtering allele frequency (the lower threshold of the 95% CI of 373/75020) of the c.3268G>A variant in JAK3 is 0.004556 for African/African American chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00447) for BA1, and therefore meets this criterion (BA1).

Approved on: 2024-04-03

Published on: 2024-04-03

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