11-118352416-C-G

Position:

• chr11-118352416-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000073.3(CD3G):​c.496C>G​(p.Arg166Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CD3G NM_000073.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD3G	NM_000073.3	c.496C>G	p.Arg166Gly	missense_variant	6/7	ENST00000532917.3	NP_000064.1
CD3G	XM_006718941.4	c.496C>G	p.Arg166Gly	missense_variant	6/7		XP_006719004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD3G	ENST00000532917.3	c.496C>G	p.Arg166Gly	missense_variant	6/7	1	NM_000073.3	ENSP00000431445.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461652 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	.;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D;T
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.3	.;M
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.067	T;D
Polyphen		1.0	.;D
Vest4		0.68
MutPred		0.83		.;Loss of stability (P = 0.0602);
MVP		0.71
MPC		1.3
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.37
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;