rs201529449

Positions:

• chr11-118352416-C-A
• chr11-118352416-C-G
• chr11-118352416-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP6 BP7 BA1

The NM_000073.3(CD3G):​c.496C>A​(p.Arg166Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 1,613,836 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0020 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (186 hom.)
• Consequence: CD3G NM_000073.3 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 1.82

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BP6: Variant 11-118352416-C-A is Benign according to our data. Variant chr11-118352416-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 541655.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
• BP7: Synonymous conserved (PhyloP=1.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD3G	NM_000073.3	c.496C>A	p.Arg166Arg	synonymous_variant	6/7	ENST00000532917.3	NP_000064.1
CD3G	XM_006718941.4	c.496C>A	p.Arg166Arg	synonymous_variant	6/7		XP_006719004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD3G	ENST00000532917.3	c.496C>A	p.Arg166Arg	synonymous_variant	6/7	1	NM_000073.3	ENSP00000431445.2

Frequencies

GnomAD3 genomes AF: 0.00201 AC: 305 AN: 152086 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00684 AC: 1719 AN: 251462 Hom.: 51 AF XY: 0.00904 AC XY: 1229 AN XY: 135902

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.0552

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00350 AC: 5116 AN: 1461632 Hom.: 186 Cov.: 31 AF XY: 0.00500 AC XY: 3633 AN XY: 727142

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0557

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000306

Gnomad4 OTH exome AF: 0.00421

GnomAD4 genome AF: 0.00198 AC: 302 AN: 152204 Hom.: 12 Cov.: 32 AF XY: 0.00318 AC XY: 237 AN XY: 74430

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0615

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000224 Hom.: 0

Bravo AF: 0.000419

Asia WGS AF: 0.0240 AC: 85 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Combined immunodeficiency due to CD3gamma deficiency Uncertain:1 Benign:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	12
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs201529449; hg19: chr11-118223131;