11-118350634-T-C

Variant names:

• chr11-118350634-T-C
• rs3753059
• NM_000073.3:c.390T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000073.3(CD3G):​c.390T>C​(p.Ala130Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,613,082 control chromosomes in the GnomAD database, including 33,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2879 hom., cov: 30)
  • Exomes 𝑓: 0.18 (30461 hom.)
• Consequence: CD3G NM_000073.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.937
• Publications: 16 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 11-118350634-T-C is Benign according to our data. Variant chr11-118350634-T-C is described in ClinVar as Benign. ClinVar VariationId is 302684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.937 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD3G	NM_000073.3	c.390T>C	p.Ala130Ala	synonymous_variant	Exon 4 of 7	ENST00000532917.3	NP_000064.1
CD3G	NM_001440319.1	c.390T>C	p.Ala130Ala	synonymous_variant	Exon 4 of 7		NP_001427248.1
CD3G	XM_005271724.5	c.390T>C	p.Ala130Ala	synonymous_variant	Exon 4 of 4		XP_005271781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD3G	ENST00000532917.3	c.390T>C	p.Ala130Ala	synonymous_variant	Exon 4 of 7	1	NM_000073.3	ENSP00000431445.2

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26845 AN: 151532 Hom.: 2884 Cov.: 30

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.169

GnomAD2 exomes AF: 0.216 AC: 54245 AN: 251442 AF XY: 0.230

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.0909

Gnomad ASJ exome AF: 0.232

Gnomad EAS exome AF: 0.502

Gnomad FIN exome AF: 0.186

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.181 AC: 264617 AN: 1461432 Hom.: 30461 Cov.: 34 AF XY: 0.190 AC XY: 138154 AN XY: 727052

African (AFR) AF: 0.158 AC: 5295 AN: 33472

American (AMR) AF: 0.0962 AC: 4303 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 6240 AN: 26124

East Asian (EAS) AF: 0.506 AC: 20080 AN: 39668

South Asian (SAS) AF: 0.452 AC: 38953 AN: 86244

European-Finnish (FIN) AF: 0.183 AC: 9758 AN: 53392

Middle Eastern (MID) AF: 0.237 AC: 1368 AN: 5764

European-Non Finnish (NFE) AF: 0.150 AC: 166351 AN: 1111674

Other (OTH) AF: 0.203 AC: 12269 AN: 60374

GnomAD4 genome AF: 0.177 AC: 26863 AN: 151650 Hom.: 2879 Cov.: 30 AF XY: 0.185 AC XY: 13740 AN XY: 74072

African (AFR) AF: 0.157 AC: 6489 AN: 41358

American (AMR) AF: 0.122 AC: 1868 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3466

East Asian (EAS) AF: 0.503 AC: 2573 AN: 5114

South Asian (SAS) AF: 0.465 AC: 2214 AN: 4766

European-Finnish (FIN) AF: 0.186 AC: 1963 AN: 10538

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.154 AC: 10415 AN: 67844

Other (OTH) AF: 0.173 AC: 364 AN: 2108

Alfa AF: 0.160 Hom.: 1945

Bravo AF: 0.167

EpiCase AF: 0.166

EpiControl AF: 0.164

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Combined immunodeficiency due to CD3gamma deficiency Benign:3

Feb 07, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 26, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.7
DANN	Benign	0.68
PhyloP100		0.94
Mutation Taster		=99/1	polymorphism (auto)

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: rs3753059; hg19: chr11-118221349; COSMIC: COSV52676182; COSMIC: COSV52676182;