rs3753059

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:6
• 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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

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.

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.390T>C	p.Ala130Ala	synonymous	Exon 4 of 7	NP_000064.1	P09693
	CD3G	NM_001440319.1		c.390T>C	p.Ala130Ala	synonymous	Exon 4 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.390T>C	p.Ala130Ala	synonymous	Exon 4 of 7	ENSP00000431445.2	P09693
	CD3G	ENST00000292144.8	TSL:1	n.*447T>C		non_coding_transcript_exon	Exon 5 of 8	ENSP00000292144.4	J3KNA5
	CD3G	ENST00000292144.8	TSL:1	n.*447T>C		3_prime_UTR	Exon 5 of 8	ENSP00000292144.4	J3KNA5

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Combined immunodeficiency due to CD3gamma deficiency (3)
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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;