chr11-118350635-G-C

Position:

• chr11-118350635-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000073.3(CD3G):​c.391G>C​(p.Val131Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V131F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: CD3G NM_000073.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.224

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.104917854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD3G	NM_000073.3	c.391G>C	p.Val131Leu	missense_variant	4/7	ENST00000532917.3	NP_000064.1
CD3G	XM_005271724.5	c.391G>C	p.Val131Leu	missense_variant	4/4		XP_005271781.1
CD3G	XM_006718941.4	c.391G>C	p.Val131Leu	missense_variant	4/7		XP_006719004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD3G	ENST00000532917.3	c.391G>C	p.Val131Leu	missense_variant	4/7	1	NM_000073.3	ENSP00000431445.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.1
DANN	Benign	0.53
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.79	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.047
Sift	Benign	0.77	T
Sift4G	Benign	0.64	T
Polyphen		0.058	B
Vest4		0.22
MutPred		0.27		Loss of catalytic residue at G132 (P = 0.2039);
MVP		0.61
MPC		0.35
ClinPred		0.082	T
GERP RS		1.6
Varity_R		0.14
gMVP		0.35

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: rs3753058; hg19: chr11-118221350;