Genetic Variant SH2D3A:p.Thr272Thr (chr19-6754996-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005490.3(SH2D3A):c.816A>G(p.Thr272Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,613,586 control chromosomes in the GnomAD database, including 71,201 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 0.34 ( 9470 hom., cov: 30)

Exomes 𝑓: 0.29 ( 61731 hom. )

Consequence

SH2D3A
NM_005490.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.145

Publications

29 publications found

Variant links:

Genes affected

SH2D3A (HGNC:16885): (SH2 domain containing 3A) Predicted to enable guanyl-nucleotide exchange factor activity and phosphotyrosine residue binding activity. Predicted to be involved in positive regulation of peptidyl-serine phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

SH2D3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP7

Synonymous conserved (PhyloP=0.145 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2D3A	NM_005490.3 link	c.816A>G	p.Thr272Thr	synonymous_variant	Exon 5 of 10	ENST00000245908.11	NP_005481.2	Q9BRG2-1A8K2M8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2D3A	ENST00000245908.11 link	c.816A>G	p.Thr272Thr	synonymous_variant	Exon 5 of 10	1	NM_005490.3	ENSP00000245908.5		Q9BRG2-1

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51745

AN:

151736

Hom.:

9451

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.293

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.319

GnomAD2 exomes

AF:

0.299

AC:

75022

AN:

250580

AF XY:

0.291

show subpopulations

Gnomad AFR exome

AF:

0.465

Gnomad AMR exome

AF:

0.294

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.324

Gnomad FIN exome

AF:

0.364

Gnomad NFE exome

AF:

0.295

Gnomad OTH exome

AF:

0.296

GnomAD4 exome

AF:

0.287

AC:

419921

AN:

1461732

Hom.:

61731

Cov.:

AF XY:

0.284

AC XY:

206307

AN XY:

727154

show subpopulations

African (AFR)

AF:

0.461

AC:

15446

AN:

33480

American (AMR)

AF:

0.295

AC:

13212

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

6114

AN:

26136

East Asian (EAS)

AF:

0.300

AC:

11929

AN:

39700

South Asian (SAS)

AF:

0.203

AC:

17514

AN:

86258

European-Finnish (FIN)

AF:

0.362

AC:

19275

AN:

53274

Middle Eastern (MID)

AF:

0.259

AC:

1494

AN:

5768

European-Non Finnish (NFE)

AF:

0.285

AC:

317293

AN:

1112000

Other (OTH)

AF:

0.292

AC:

17644

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

19499

38998

58498

77997

97496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10486

20972

31458

41944

52430

<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:

0.341

AC:

51816

AN:

151854

Hom.:

9470

Cov.:

AF XY:

0.342

AC XY:

25384

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.458

AC:

18950

AN:

41372

American (AMR)

AF:

0.303

AC:

4628

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

775

AN:

3466

East Asian (EAS)

AF:

0.326

AC:

1681

AN:

5156

South Asian (SAS)

AF:

0.201

AC:

965

AN:

4812

European-Finnish (FIN)

AF:

0.377

AC:

3981

AN:

10546

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.292

AC:

19810

AN:

67910

Other (OTH)

AF:

0.322

AC:

678

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1658

3316

4974

6632

8290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.299

Hom.:

30587

Bravo

AF:

0.343

Asia WGS

AF:

0.277

AC:

965

AN:

3478

EpiCase

AF:

0.274

EpiControl

AF:

0.283

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.1

(source)

DANN

Benign

0.51

PhyloP100

0.14

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over