Genetic Variant NM_005490.3:c.1655C>T (chr19-6752669-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005490.3(SH2D3A):c.1655C>T(p.Ala552Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,401,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A552G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SH2D3A
NM_005490.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0630

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08529028).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005490.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH2D3A	NM_005490.3	MANE Select	c.1655C>T	p.Ala552Val	missense	Exon 10 of 10	NP_005481.2	Q9BRG2-1
SH2D3A	NM_001439225.1		c.1742C>T	p.Ala581Val	missense	Exon 9 of 9	NP_001426154.1
SH2D3A	NM_001386585.1		c.1652C>T	p.Ala551Val	missense	Exon 10 of 10	NP_001373514.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH2D3A	ENST00000245908.11	TSL:1 MANE Select	c.1655C>T	p.Ala552Val	missense	Exon 10 of 10	ENSP00000245908.5	Q9BRG2-1
SH2D3A	ENST00000892014.1		c.1742C>T	p.Ala581Val	missense	Exon 9 of 9	ENSP00000562073.1
SH2D3A	ENST00000892016.1		c.1739C>T	p.Ala580Val	missense	Exon 9 of 9	ENSP00000562075.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000644

AC:

AN:

155244

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000403

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1401750

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

691676

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31828

American (AMR)

AF:

0.0000278

AC:

AN:

35986

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.00

AC:

AN:

36086

South Asian (SAS)

AF:

0.00

AC:

AN:

79444

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1080934

Other (OTH)

AF:

0.00

AC:

AN:

58110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0052

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.68

M_CAP

Benign

0.0059

MetaRNN

Benign

0.085

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

0.063

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.81

REVEL

Benign

0.098

Sift

Benign

0.82

Sift4G

Pathogenic

0.0

Polyphen

0.91

Vest4

0.079

MutPred

0.14

Loss of methylation at R548 (P = 0.0967)

MVP

0.56

MPC

1.4

ClinPred

0.26

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.028

gMVP

0.36

Mutation Taster

=94/6

polymorphism

(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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over