11-118350635-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000532917.3(CD3G):c.391G>T(p.Val131Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,613,004 control chromosomes in the GnomAD database, including 33,336 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. V131V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.18 ( 2877 hom., cov: 30)

Exomes 𝑓: 0.18 ( 30459 hom. )

Consequence

CD3G
ENST00000532917.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.224

Publications

30 publications found

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 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

CD3G links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038505793).

BP6

Variant 11-118350635-G-T is Benign according to our data. Variant chr11-118350635-G-T is described in ClinVar as Benign. ClinVar VariationId is 302685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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: ENST00000532917.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD3G	NM_000073.3	MANE Select	c.391G>T	p.Val131Phe	missense	Exon 4 of 7	NP_000064.1
	CD3G	NM_001440319.1		c.391G>T	p.Val131Phe	missense	Exon 4 of 7	NP_001427248.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CD3G	ENST00000532917.3	TSL:1 MANE Select	c.391G>T	p.Val131Phe	missense	Exon 4 of 7	ENSP00000431445.2
CD3G	ENST00000292144.8	TSL:1	n.*448G>T		non_coding_transcript_exon	Exon 5 of 8	ENSP00000292144.4
CD3G	ENST00000292144.8	TSL:1	n.*448G>T		3_prime_UTR	Exon 5 of 8	ENSP00000292144.4

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26825

AN:

151538

Hom.:

2882

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.122

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:

54240

AN:

251440

AF XY:

0.230

show subpopulations

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:

264603

AN:

1461348

Hom.:

30459

Cov.:

AF XY:

0.190

AC XY:

138146

AN XY:

726996

show subpopulations

African (AFR)

AF:

0.158

AC:

5294

AN:

33470

American (AMR)

AF:

0.0962

AC:

4303

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

6239

AN:

26122

East Asian (EAS)

AF:

0.506

AC:

20078

AN:

39668

South Asian (SAS)

AF:

0.452

AC:

38956

AN:

86194

European-Finnish (FIN)

AF:

0.183

AC:

9759

AN:

53392

Middle Eastern (MID)

AF:

0.237

AC:

1368

AN:

5764

European-Non Finnish (NFE)

AF:

0.150

AC:

166337

AN:

1111644

Other (OTH)

AF:

0.203

AC:

12269

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

11564

23128

34691

46255

57819

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6284

12568

18852

25136

31420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.177

AC:

26843

AN:

151656

Hom.:

2877

Cov.:

AF XY:

0.185

AC XY:

13734

AN XY:

74092

show subpopulations

African (AFR)

AF:

0.157

AC:

6488

AN:

41372

American (AMR)

AF:

0.122

AC:

1864

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

801

AN:

3464

East Asian (EAS)

AF:

0.503

AC:

2572

AN:

5112

South Asian (SAS)

AF:

0.465

AC:

2212

AN:

4756

European-Finnish (FIN)

AF:

0.186

AC:

1964

AN:

10538

Middle Eastern (MID)

AF:

0.199

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.153

AC:

10403

AN:

67860

Other (OTH)

AF:

0.173

AC:

363

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

927

1855

2782

3710

4637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

312

624

936

1248

1560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.173

Hom.:

6067

Bravo

AF:

0.167

TwinsUK

AF:

0.142

AC:

525

ALSPAC

AF:

0.155

AC:

599

ESP6500AA

AF:

0.00432

AC:

ESP6500EA

AF:

0.00442

AC:

ExAC

AF:

0.219

AC:

26586

Asia WGS

AF:

0.447

AC:

1554

AN:

3478

EpiCase

AF:

0.166

EpiControl

AF:

0.164

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Combined immunodeficiency due to CD3gamma deficiency (3)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.61

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.6

PhyloP100

0.22

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.29

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0090

Polyphen

0.99

Vest4

0.25

MPC

1.1

ClinPred

0.022

GERP RS

1.6

Varity_R

0.45

gMVP

0.61

Mutation Taster

=90/10

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over