rs483352927

Positions:

• chr11-118349740-CAGGAAACCACTTGGTTA-C

Variant summary

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

The ENST00000528540(CD3G):​c.-84-16_-84delAAACCACTTGGTTAAGG variant causes a splice acceptor, splice region, 5 prime UTR, intron 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 ENST00000528540 splice_acceptor, splice_region, 5_prime_UTR, intron
• 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]

CD3G (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 3.5151515 fraction of the gene. Cryptic splice site detected, with MaxEntScore 11, offset of 0 (no position change), new splice context is: cacggcttttctcatttcAGgtg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• 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/exons	MANE	Protein	UniProt
CD3G	NM_000073.3	c.81_97delAAACCACTTGGTTAAGG	p.Asn28fs	frameshift_variant, splice_region_variant	3/7	ENST00000532917.3	NP_000064.1
CD3G	XM_005271724.5	c.81_97delAAACCACTTGGTTAAGG	p.Asn28fs	frameshift_variant, splice_region_variant	3/4		XP_005271781.1
CD3G	XM_006718941.4	c.81_97delAAACCACTTGGTTAAGG	p.Asn28fs	frameshift_variant, splice_region_variant	3/7		XP_006719004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD3G	ENST00000532917.3	c.81_97delAAACCACTTGGTTAAGG	p.Asn28fs	frameshift_variant, splice_region_variant	3/7	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

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 20, 1992

- -

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;