rs181713283

Variant names:

• chr11-118344459-G-A
• rs181713283
• NM_000073.3:c.36G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_000073.3(CD3G):​c.36G>A​(p.Leu12Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,570,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: CD3G NM_000073.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.20
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-118344459-G-A is Benign according to our data. Variant chr11-118344459-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 649896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.2 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000159 (225/1418246) while in subpopulation MID AF = 0.0021 (12/5710). AF 95% confidence interval is 0.00121. There are 0 homozygotes in GnomAdExome4. There are 123 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD3G	NM_000073.3	c.36G>A	p.Leu12Leu	synonymous_variant	Exon 1 of 7	ENST00000532917.3	NP_000064.1
CD3G	NM_001440319.1	c.36G>A	p.Leu12Leu	synonymous_variant	Exon 1 of 7		NP_001427248.1
CD3G	XM_005271724.5	c.36G>A	p.Leu12Leu	synonymous_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.36G>A	p.Leu12Leu	synonymous_variant	Exon 1 of 7	1	NM_000073.3	ENSP00000431445.2

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000258 AC: 47 AN: 182044 AF XY: 0.000280

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000413

Gnomad ASJ exome AF: 0.000571

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000184

Gnomad OTH exome AF: 0.00103

GnomAD4 exome AF: 0.000159 AC: 225 AN: 1418246 Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 123 AN XY: 701036

African (AFR) AF: 0.000274 AC: 9 AN: 32788

American (AMR) AF: 0.000637 AC: 24 AN: 37684

Ashkenazi Jewish (ASJ) AF: 0.000633 AC: 16 AN: 25296

East Asian (EAS) AF: 0.00 AC: 0 AN: 37856

South Asian (SAS) AF: 0.000348 AC: 28 AN: 80436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50546

Middle Eastern (MID) AF: 0.00210 AC: 12 AN: 5710

European-Non Finnish (NFE) AF: 0.000107 AC: 116 AN: 1089158

Other (OTH) AF: 0.000340 AC: 20 AN: 58772

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74504

African (AFR) AF: 0.0000240 AC: 1 AN: 41584

American (AMR) AF: 0.000588 AC: 9 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000147 Hom.: 0

Bravo AF: 0.000227

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Combined immunodeficiency due to CD3gamma deficiency Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jan 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.5
DANN	Benign	0.66
PhyloP100		2.2
PromoterAI		-0.067	Neutral
Mutation Taster		=295/5	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: rs181713283; hg19: chr11-118215174;