11-118344439-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000073.3(CD3G):​c.16G>A​(p.Gly6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,419,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. G6R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CD3G NM_000073.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08935055).

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>A	p.Gly6Ser	missense	Exon 1 of 7	NP_000064.1	P09693
	CD3G	NM_001440319.1		c.16G>A	p.Gly6Ser	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>A	p.Gly6Ser	missense	Exon 1 of 7	ENSP00000431445.2	P09693
	CD3G	ENST00000528540.5	TSL:1	c.-148G>A		5_prime_UTR	Exon 1 of 3	ENSP00000498162.1	A0A3B3IUD8
	CD3G	ENST00000292144.8	TSL:1	n.16G>A		non_coding_transcript_exon	Exon 1 of 8	ENSP00000292144.4	J3KNA5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000539 AC: 1 AN: 185372 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000205

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1419636 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 701844

African (AFR) AF: 0.00 AC: 0 AN: 32840

American (AMR) AF: 0.00 AC: 0 AN: 37886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25300

East Asian (EAS) AF: 0.0000263 AC: 1 AN: 37990

South Asian (SAS) AF: 0.00 AC: 0 AN: 80506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1089966

Other (OTH) AF: 0.0000170 AC: 1 AN: 58838

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	10
DANN	Benign	0.93
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.18
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.13
Sift	Benign	0.47	T
Sift4G	Benign	0.40	T
Polyphen		0.42	B
Vest4		0.28
MutPred		0.36		Loss of catalytic residue at G6 (P = 0.0024)
MVP		0.65
MPC		0.51
ClinPred		0.18	T
GERP RS		0.96
PromoterAI		-0.028	Neutral
Varity_R		0.039
gMVP		0.51
Mutation Taster		=88/12	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;