Genetic Variant CD3G:c.439+76G>A (chr11-118350759-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000073.3(CD3G):c.439+76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,607,790 control chromosomes in the GnomAD database, including 88,238 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8141 hom., cov: 28)

Exomes 𝑓: 0.32 ( 80097 hom. )

Consequence

CD3G
NM_000073.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.183

Publications

17 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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

CD3G links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 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.439+76G>A		intron	N/A	NP_000064.1	P09693
	CD3G	NM_001440319.1		c.439+76G>A		intron	N/A	NP_001427248.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD3G	ENST00000532917.3	TSL:1 MANE Select	c.439+76G>A	intron	N/A	ENSP00000431445.2	P09693
CD3G	ENST00000292144.8	TSL:1	n.*496+76G>A	intron	N/A	ENSP00000292144.4	J3KNA5
CD3G	ENST00000901817.1		c.439+76G>A	intron	N/A	ENSP00000571876.1

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48505

AN:

151050

Hom.:

8135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.324

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.577

Gnomad SAS

AF:

0.527

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.306

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.297

GnomAD4 exome

AF:

0.323

AC:

470114

AN:

1456622

Hom.:

80097

Cov.:

AF XY:

0.329

AC XY:

238467

AN XY:

724684

show subpopulations

African (AFR)

AF:

0.324

AC:

10820

AN:

33388

American (AMR)

AF:

0.207

AC:

9221

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

9205

AN:

26012

East Asian (EAS)

AF:

0.580

AC:

22855

AN:

39398

South Asian (SAS)

AF:

0.520

AC:

44681

AN:

85890

European-Finnish (FIN)

AF:

0.305

AC:

15837

AN:

51946

Middle Eastern (MID)

AF:

0.328

AC:

1693

AN:

5160

European-Non Finnish (NFE)

AF:

0.302

AC:

335450

AN:

1110108

Other (OTH)

AF:

0.339

AC:

20352

AN:

60118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

14613

29226

43840

58453

73066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11328

22656

33984

45312

56640

<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:

0.321

AC:

48552

AN:

151168

Hom.:

8141

Cov.:

AF XY:

0.328

AC XY:

24197

AN XY:

73846

show subpopulations

African (AFR)

AF:

0.325

AC:

13356

AN:

41120

American (AMR)

AF:

0.253

AC:

3839

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1200

AN:

3456

East Asian (EAS)

AF:

0.577

AC:

2952

AN:

5114

South Asian (SAS)

AF:

0.526

AC:

2487

AN:

4728

European-Finnish (FIN)

AF:

0.320

AC:

3354

AN:

10474

Middle Eastern (MID)

AF:

0.298

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.302

AC:

20473

AN:

67784

Other (OTH)

AF:

0.299

AC:

631

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1495

2991

4486

5982

7477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

500

1000

1500

2000

2500

<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:

0.306

Hom.:

12345

Bravo

AF:

0.313

Asia WGS

AF:

0.529

AC:

1839

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.2

(source)

DANN

Benign

0.40

PhyloP100

0.18

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over