NM_018957.6:c.700C>G

Variant names:

• chr22-37644882-C-G
• rs960519170
• NM_018957.6:c.700C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018957.6(SH3BP1):​c.700C>G​(p.Gln234Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000212 in 1,461,722 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: SH3BP1 NM_018957.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.58
• Publications: 0 publications found

Genes affected

SH3BP1 (HGNC:10824): (SH3 domain binding protein 1) This gene encodes a member of the Rho GTPase activating protein (RhoGAP) family. The encoded protein regulates Rac signaling and plays a role in cytoskeletal dynamics, cell motility and epithelial junction formation. This protein's association with the exocyst complex, which tethers secretory vesicles to the plasma membrane, has been demonstrated to be important in cell motility. In a distinct complex, this protein has been shown to regulate epithelial junction formation and morphogenesis. By interacting with the Plexin-D1 cell surface receptor, this protein mediates changes in the cytoskeleton in response to semaphorin binding. This protein may promote metastasis in human liver cancer cells and tissues. [provided by RefSeq, Mar 2017]

ENSG00000285304 (HGNC:):

PDXP-DT (HGNC:40525): (PDXP divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018957.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP1	NM_018957.6	MANE Select	c.700C>G	p.Gln234Glu	missense	Exon 9 of 18	NP_061830.3
	SH3BP1	NM_001350055.2		c.700C>G	p.Gln234Glu	missense	Exon 9 of 18	NP_001336984.1
	PDXP-DT	NR_109952.1		n.678-1121G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP1	ENST00000649765.2	MANE Select	c.700C>G	p.Gln234Glu	missense	Exon 9 of 18	ENSP00000497104.1	Q9Y3L3-1
	ENSG00000285304	ENST00000451997.6	TSL:2	c.508C>G	p.Gln170Glu	missense	Exon 8 of 17	ENSP00000401076.2
	SH3BP1	ENST00000905665.1		c.700C>G	p.Gln234Glu	missense	Exon 9 of 18	ENSP00000575724.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461722 Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13 AN XY: 727158

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1111982

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		5.6
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.86
MutPred		0.70		Gain of loop (P = 0.1069)
MVP		0.80
MPC		0.60
ClinPred		0.98	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.77
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs960519170; hg19: chr22-38040889;