4-2818233-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000511747.6(SH3BP2):ā€‹c.10T>Gā€‹(p.Ser4Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SH3BP2
ENST00000511747.6 missense

Scores

1
1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.58
Variant links:
Genes affected
SH3BP2 (HGNC:10825): (SH3 domain binding protein 2) The protein encoded by this gene has an N-terminal pleckstrin homology (PH) domain, an SH3-binding proline-rich region, and a C-terminal SH2 domain. The protein binds to the SH3 domains of several proteins including the ABL1 and SYK protein tyrosine kinases , and functions as a cytoplasmic adaptor protein to positively regulate transcriptional activity in T, natural killer (NK), and basophilic cells. Mutations in this gene result in cherubism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.034372687).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SH3BP2NM_001122681.2 linkuse as main transcriptc.-4-2381T>G intron_variant ENST00000503393.8 NP_001116153.1
SH3BP2NM_001145856.2 linkuse as main transcriptc.10T>G p.Ser4Ala missense_variant 1/13 NP_001139328.1
SH3BP2NM_001145855.2 linkuse as main transcriptc.81-2381T>G intron_variant NP_001139327.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SH3BP2ENST00000503393.8 linkuse as main transcriptc.-4-2381T>G intron_variant 1 NM_001122681.2 ENSP00000422168 P2P78314-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
839492
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
388416
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.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 09, 2021The c.10T>G (p.S4A) alteration is located in exon 1 (coding exon 1) of the SH3BP2 gene. This alteration results from a T to G substitution at nucleotide position 10, causing the serine (S) at amino acid position 4 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
8.1
DANN
Benign
0.85
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0019
N
LIST_S2
Benign
0.15
T
M_CAP
Uncertain
0.22
D
MetaRNN
Benign
0.034
T
MetaSVM
Benign
-0.93
T
MutationTaster
Benign
1.0
N;N;N;N;N;N
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
0.13
N
REVEL
Benign
0.22
Sift
Benign
1.0
T
Vest4
0.083
MutPred
0.20
Loss of phosphorylation at S4 (P = 0.0014);
MVP
0.27
MPC
0.13
ClinPred
0.038
T
GERP RS
-1.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-2819960; API