4-2829843-G-T

Variant names:

• chr4-2829843-G-T
• NM_001122681.2:c.937G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001122681.2(SH3BP2):​c.937G>T​(p.Gly313Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G313R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SH3BP2 NM_001122681.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BP2	NM_001122681.2	c.937G>T	p.Gly313Trp	missense_variant	Exon 8 of 13	ENST00000503393.8	NP_001116153.1
SH3BP2	NM_001145856.2	c.1108G>T	p.Gly370Trp	missense_variant	Exon 8 of 13		NP_001139328.1
SH3BP2	NM_001145855.2	c.1021G>T	p.Gly341Trp	missense_variant	Exon 8 of 13		NP_001139327.1
SH3BP2	NM_003023.4	c.937G>T	p.Gly313Trp	missense_variant	Exon 8 of 13		NP_003014.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3BP2	ENST00000503393.8	c.937G>T	p.Gly313Trp	missense_variant	Exon 8 of 13	1	NM_001122681.2	ENSP00000422168.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;.;T;T;.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.78	.;T;.;.;T;T
M_CAP	Pathogenic	0.77	D
MetaRNN	Uncertain	0.69	D;D;D;D;D;D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Uncertain	2.1	M;.;M;M;.;M
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N
REVEL	Uncertain	0.41
Sift	Uncertain	0.0030	D;D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D;D
Polyphen		1.0	D;.;D;D;.;D
Vest4		0.63
MutPred		0.47		Loss of helix (P = 0.0076);.;Loss of helix (P = 0.0076);Loss of helix (P = 0.0076);.;Loss of helix (P = 0.0076);
MVP		0.89
MPC		0.74
ClinPred		0.58	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.051

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr4-2831570;