11-118344460-G-C

Variant names:

• chr11-118344460-G-C
• rs1948336348
• NM_000073.3:c.37G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000073.3(CD3G):​c.37G>C​(p.Ala13Pro) 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 pathogenic 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. A13V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD3G NM_000073.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.917
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• combined immunodeficiency due to CD3gamma deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD3G	NM_000073.3	c.37G>C	p.Ala13Pro	missense_variant	Exon 1 of 7	ENST00000532917.3	NP_000064.1
CD3G	NM_001440319.1	c.37G>C	p.Ala13Pro	missense_variant	Exon 1 of 7		NP_001427248.1
CD3G	XM_005271724.5	c.37G>C	p.Ala13Pro	missense_variant	Exon 1 of 4		XP_005271781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD3G	ENST00000532917.3	c.37G>C	p.Ala13Pro	missense_variant	Exon 1 of 7	1	NM_000073.3	ENSP00000431445.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	20
DANN	Benign	0.87
DEOGEN2	Uncertain	0.57	D
Eigen	Benign	0.18
Eigen_PC	Benign	0.047
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.92
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.043	D
Polyphen		0.98	D
Vest4		0.74
MutPred		0.54		Loss of stability (P = 0.1365);
MVP		0.80
MPC		1.1
ClinPred		0.89	D
GERP RS		3.6
PromoterAI		0.0040	Neutral
Varity_R		0.52
gMVP		0.71
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs1948336348; hg19: chr11-118215175;