NM_000073.3:c.81_97delAAACCACTTGGTTAAGG

Variant names:

• chr11-118349740-CAGGAAACCACTTGGTTA-C
• rs483352927
• NM_000073.3:c.81_97delAAACCACTTGGTTAAGG

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_000073.3(CD3G):​c.81_97delAAACCACTTGGTTAAGG​(p.Asn28fs) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CD3G NM_000073.3 frameshift, splice_region
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.97

Genes affected

CD3G (HGNC:1675): (CD3 gamma subunit of T-cell receptor complex) The protein encoded by this gene is the CD3-gamma polypeptide, which together with CD3-epsilon, -delta and -zeta, and the T-cell receptor alpha/beta and gamma/delta heterodimers, forms the T-cell receptor-CD3 complex. This complex plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. The genes encoding the epsilon, gamma and delta polypeptides are located in the same cluster on chromosome 11. Defects in this gene are associated with T cell immunodeficiency. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.852 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-118349740-CAGGAAACCACTTGGTTA-C is Pathogenic according to our data. Variant chr11-118349740-CAGGAAACCACTTGGTTA-C is described in ClinVar as [Pathogenic]. Clinvar id is 12754.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD3G	NM_000073.3	c.81_97delAAACCACTTGGTTAAGG	p.Asn28fs	frameshift_variant, splice_region_variant	Exon 3 of 7	ENST00000532917.3	NP_000064.1
CD3G	XM_005271724.5	c.81_97delAAACCACTTGGTTAAGG	p.Asn28fs	frameshift_variant, splice_region_variant	Exon 3 of 4		XP_005271781.1
CD3G	XM_006718941.4	c.81_97delAAACCACTTGGTTAAGG	p.Asn28fs	frameshift_variant, splice_region_variant	Exon 3 of 7		XP_006719004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD3G	ENST00000532917.3	c.81_97delAAACCACTTGGTTAAGG	p.Asn28fs	frameshift_variant, splice_region_variant	Exon 3 of 7	1	NM_000073.3	ENSP00000431445.2

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Combined immunodeficiency due to CD3gamma deficiency Pathogenic:1

Aug 20, 1992

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs483352927; hg19: chr11-118220455;