Variant 2-235040897-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014521.3(SH3BP4):c.128C>A(p.Pro43His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000844 in 1,610,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

SH3BP4
NM_014521.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.66

Variant links:

Genes affected

SH3BP4 (HGNC:10826): (SH3 domain binding protein 4) This gene encodes a protein with 3 Asn-Pro-Phe (NPF) motifs, an SH3 domain, a PXXP motif, a bipartite nuclear targeting signal, and a tyrosine phosphorylation site. This protein is involved in cargo-specific control of clathrin-mediated endocytosis, specifically controlling the internalization of a specific protein receptor. [provided by RefSeq, Jul 2008]

SH3BP4 links:

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=0.3810741).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3BP4	NM_014521.3 linkuse as main transcript	c.128C>A	p.Pro43His	missense_variant	4/6	ENST00000392011.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BP4	ENST00000392011.7 linkuse as main transcript	c.128C>A	p.Pro43His	missense_variant	4/6	1	NM_014521.3	P1	Q9P0V3-1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.0000956

AC:

AN:

250994

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000202

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:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000761

AC:

111

AN:

1458466

Hom.:

Cov.:

AF XY:

0.0000828

AC XY:

AN XY:

724742

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000336

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:

0.0000667

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000164

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.0000772

Hom.:

Bravo

AF:

0.000144

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.128C>A (p.P43H) alteration is located in exon 4 (coding exon 2) of the SH3BP4 gene. This alteration results from a C to A substitution at nucleotide position 128, causing the proline (P) at amino acid position 43 to be replaced by a histidine (H). 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

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

T;T;T;T;T;.;.

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.019

MetaRNN

Benign

0.38

T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.9

L;.;L;L;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.4

N;N;N;N;D;D;D

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D

Polyphen

1.0

D;.;D;D;.;.;.

Vest4

0.86

MVP

0.62

MPC

0.96

ClinPred

0.24

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.48

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over