chr4-2829709-C-T

Position:

• chr4-2829709-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001122681.2(SH3BP2):​c.803C>T​(p.Pro268Leu) 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SH3BP2 NM_001122681.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

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]

ACMG classification

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=0.053270787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3BP2	NM_001122681.2	c.803C>T	p.Pro268Leu	missense_variant	8/13	ENST00000503393.8	NP_001116153.1
SH3BP2	NM_001145856.2	c.974C>T	p.Pro325Leu	missense_variant	8/13		NP_001139328.1
SH3BP2	NM_001145855.2	c.887C>T	p.Pro296Leu	missense_variant	8/13		NP_001139327.1
SH3BP2	NM_003023.4	c.803C>T	p.Pro268Leu	missense_variant	8/13		NP_003014.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3BP2	ENST00000503393.8	c.803C>T	p.Pro268Leu	missense_variant	8/13	1	NM_001122681.2	ENSP00000422168	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	0.24
DANN	Benign	0.40
DEOGEN2	Benign	0.10	T;.;T;T;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.73	.;T;.;.;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.053	T;T;T;T;T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	0.20	N;.;N;N;.;N
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	0.40	T;T;T;T;T;T
Polyphen		0.0010	B;.;B;B;.;B
Vest4		0.057
MutPred		0.24		Gain of MoRF binding (P = 0.0756);.;Gain of MoRF binding (P = 0.0756);Gain of MoRF binding (P = 0.0756);.;Gain of MoRF binding (P = 0.0756);
MVP		0.73
MPC		0.17
ClinPred		0.022	T
GERP RS		-0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.017

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

Other links and lift over

dbSNP: rs148592718; hg19: chr4-2831436;