rs763958239

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005490.3(SH2D3A):​c.1630C>T​(p.Leu544Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. L544V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SH2D3A
NM_005490.3 missense

Scores

1
8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.61
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38100797).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SH2D3ANM_005490.3 linkc.1630C>T p.Leu544Phe missense_variant Exon 10 of 10 ENST00000245908.11 NP_005481.2 Q9BRG2-1A8K2M8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SH2D3AENST00000245908.11 linkc.1630C>T p.Leu544Phe missense_variant Exon 10 of 10 1 NM_005490.3 ENSP00000245908.5 Q9BRG2-1
SH2D3AENST00000437152.7 linkc.1351C>T p.Leu451Phe missense_variant Exon 8 of 8 2 ENSP00000393303.2 Q9BRG2-2
SH2D3AENST00000597168.1 linkn.444-466C>T intron_variant Intron 2 of 2 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000654
AC:
1
AN:
153018
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
81788
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000231
GnomAD4 exome
AF:
7.14e-7
AC:
1
AN:
1400346
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
690830
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Uncertain
0.091
D
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
.;T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.70
T;T
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.38
T;T
MetaSVM
Benign
-0.47
T
MutationAssessor
Uncertain
2.3
.;M
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-3.4
D;D
REVEL
Benign
0.24
Sift
Uncertain
0.029
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.91
.;P
Vest4
0.26
MutPred
0.45
.;Loss of stability (P = 0.1281);
MVP
0.86
MPC
2.6
ClinPred
0.94
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.15
gMVP
0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs763958239; hg19: chr19-6752705; API