rs139781104

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000073.3(CD3G):c.64G>A(p.Ala22Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000468 in 1,614,030 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

CD3G
NM_000073.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.70

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063080788).

BP6

Variant 11-118349035-G-A is Benign according to our data. Variant chr11-118349035-G-A is described in ClinVar as [Benign]. Clinvar id is 474800.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00273 (416/152190) while in subpopulation AFR AF= 0.00954 (396/41516). AF 95% confidence interval is 0.00876. There are 4 homozygotes in gnomad4. There are 190 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CD3G	NM_000073.3 linkuse as main transcript	c.64G>A	p.Ala22Thr	missense_variant	2/7	ENST00000532917.3
CD3G	XM_005271724.5 linkuse as main transcript	c.64G>A	p.Ala22Thr	missense_variant	2/4
CD3G	XM_006718941.4 linkuse as main transcript	c.64G>A	p.Ala22Thr	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD3G	ENST00000532917.3 linkuse as main transcript	c.64G>A	p.Ala22Thr	missense_variant	2/7	1	NM_000073.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

415

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00954

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000696

AC:

175

AN:

251434

Hom.:

AF XY:

0.000567

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00960

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000232

AC:

339

AN:

1461840

Hom.:

Cov.:

AF XY:

0.000220

AC XY:

160

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00866

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.00273

AC:

416

AN:

152190

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

190

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00954

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000408

Hom.:

Bravo

AF:

0.00289

ESP6500AA

AF:

0.00659

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000815

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Combined immunodeficiency due to CD3gamma deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.38

Eigen

Benign

-0.086

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0063

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.2

REVEL

Benign

0.23

Sift

Benign

0.057

Sift4G

Benign

0.58

Polyphen

0.68

Vest4

0.34

MVP

0.79

MPC

0.36

ClinPred

0.042

GERP RS

5.4

Varity_R

0.071

gMVP

0.36

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over