11-118344439-G-C

Variant names:

• chr11-118344439-G-C
• rs1481255896
• NM_000073.3:c.16G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000073.3(CD3G):​c.16G>C​(p.Gly6Arg) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD3G NM_000073.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.182
• Publications: 1 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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048751414).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000073.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD3G	NM_000073.3	MANE Select	c.16G>C	p.Gly6Arg	missense	Exon 1 of 7	NP_000064.1	P09693
	CD3G	NM_001440319.1		c.16G>C	p.Gly6Arg	missense	Exon 1 of 7	NP_001427248.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD3G	ENST00000532917.3	TSL:1 MANE Select	c.16G>C	p.Gly6Arg	missense	Exon 1 of 7	ENSP00000431445.2	P09693
	CD3G	ENST00000528540.5	TSL:1	c.-148G>C		5_prime_UTR	Exon 1 of 3	ENSP00000498162.1	A0A3B3IUD8
	CD3G	ENST00000292144.8	TSL:1	n.16G>C		non_coding_transcript_exon	Exon 1 of 8	ENSP00000292144.4	J3KNA5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Combined immunodeficiency due to CD3gamma deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	10
DANN	Benign	0.92
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.18
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.13
Sift	Benign	0.35	T
Sift4G	Benign	0.35	T
Polyphen		0.012	B
Vest4		0.16
MutPred		0.35		Loss of catalytic residue at G6 (P = 0.0141)
MVP		0.59
MPC		0.41
ClinPred		0.11	T
GERP RS		0.96
PromoterAI		-0.012	Neutral
Varity_R		0.053
gMVP		0.52
Mutation Taster		=84/16	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: rs1481255896; hg19: chr11-118215154;