Genetic Variant SH3BP2:p.Ser505Tyr (chr4-2833015-C-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_001122681.2(SH3BP2):c.1514C>A(p.Ser505Tyr) 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. 15/20 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. S505C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

SH3BP2
NM_001122681.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.934

Publications

4 publications found

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]

SH3BP2 Gene-Disease associations (from GenCC):

cherubism
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

SH3BP2 links:

Genome browser will be placed here

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=0.16272873).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122681.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SH3BP2	NM_001122681.2	MANE Select	c.1514C>A	p.Ser505Tyr	missense	Exon 12 of 13	NP_001116153.1
SH3BP2	NM_001145856.2		c.1685C>A	p.Ser562Tyr	missense	Exon 12 of 13	NP_001139328.1
SH3BP2	NM_001145855.2		c.1598C>A	p.Ser533Tyr	missense	Exon 12 of 13	NP_001139327.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SH3BP2	ENST00000503393.8	TSL:1 MANE Select	c.1514C>A	p.Ser505Tyr	missense	Exon 12 of 13	ENSP00000422168.3
SH3BP2	ENST00000511747.6	TSL:1	c.1685C>A	p.Ser562Tyr	missense	Exon 12 of 13	ENSP00000424846.2
SH3BP2	ENST00000356331.10	TSL:1	n.1775C>A		non_coding_transcript_exon	Exon 12 of 13

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251438

AF XY:

0.00000736

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Uncertain

0.47

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.85

M_CAP

Benign

0.045

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.71

PhyloP100

0.93

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.4

REVEL

Benign

0.20

Sift

Benign

0.078

Sift4G

Benign

0.57

Polyphen

0.044

Vest4

0.32

MutPred

0.56

Loss of sheet (P = 3e-04)

MVP

0.84

MPC

0.23

ClinPred

0.13

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.045

Mutation Taster

=88/12

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over