dbSNP rs7258236: SH2D3A:p.Asn32Asp (chr19-6760963-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005490.3(SH2D3A):c.94A>G(p.Asn32Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,611,446 control chromosomes in the GnomAD database, including 44,770 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6235 hom., cov: 32)

Exomes 𝑓: 0.22 ( 38535 hom. )

Consequence

SH2D3A
NM_005490.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.379

Publications

28 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007875234).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2D3A	NM_005490.3 link	c.94A>G	p.Asn32Asp	missense_variant	Exon 3 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.94A>G	p.Asn32Asp	missense_variant	Exon 3 of 10	1	NM_005490.3	ENSP00000245908.5		Q9BRG2-1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40723

AN:

152038

Hom.:

6223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.424

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.0602

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.243

GnomAD2 exomes

AF:

0.218

AC:

53189

AN:

244140

AF XY:

0.221

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.132

Gnomad ASJ exome

AF:

0.189

Gnomad EAS exome

AF:

0.0649

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.203

GnomAD4 exome

AF:

0.223

AC:

326135

AN:

1459290

Hom.:

38535

Cov.:

AF XY:

0.225

AC XY:

163610

AN XY:

725710

show subpopulations

African (AFR)

AF:

0.427

AC:

14284

AN:

33432

American (AMR)

AF:

0.138

AC:

6154

AN:

44498

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

4762

AN:

26022

East Asian (EAS)

AF:

0.0668

AC:

2649

AN:

39642

South Asian (SAS)

AF:

0.292

AC:

25084

AN:

86022

European-Finnish (FIN)

AF:

0.198

AC:

10508

AN:

53140

Middle Eastern (MID)

AF:

0.263

AC:

1517

AN:

5758

European-Non Finnish (NFE)

AF:

0.223

AC:

247944

AN:

1110496

Other (OTH)

AF:

0.220

AC:

13233

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

12846

25691

38537

51382

64228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8536

17072

25608

34144

42680

<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:

0.268

AC:

40774

AN:

152156

Hom.:

6235

Cov.:

AF XY:

0.263

AC XY:

19532

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.424

AC:

17584

AN:

41502

American (AMR)

AF:

0.167

AC:

2553

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

653

AN:

3468

East Asian (EAS)

AF:

0.0601

AC:

312

AN:

5190

South Asian (SAS)

AF:

0.289

AC:

1396

AN:

4830

European-Finnish (FIN)

AF:

0.202

AC:

2137

AN:

10582

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.224

AC:

15195

AN:

67980

Other (OTH)

AF:

0.246

AC:

519

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1515

3030

4546

6061

7576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.232

Hom.:

21857

Bravo

AF:

0.270

TwinsUK

AF:

0.234

AC:

868

ALSPAC

AF:

0.214

AC:

824

ESP6500AA

AF:

0.416

AC:

1830

ESP6500EA

AF:

0.216

AC:

1858

ExAC

AF:

0.227

AC:

27542

Asia WGS

AF:

0.179

AC:

622

AN:

3478

EpiCase

AF:

0.218

EpiControl

AF:

0.219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.091

T;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.50

T;T

MetaRNN

Benign

0.0079

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.3

N;.

PhyloP100

0.38

PrimateAI

Uncertain

0.49

PROVEAN

Benign

1.4

N;.

REVEL

Benign

0.12

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.041

MPC

0.29

ClinPred

0.00069

GERP RS

3.7

Varity_R

0.053

gMVP

0.20

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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