22-37641383-C-A

Variant names:

• chr22-37641383-C-A
• rs1471015359
• NM_018957.6:c.112C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_018957.6(SH3BP1):​c.112C>A​(p.Arg38Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SH3BP1 NM_018957.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.782
• 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:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).
• BP7: Synonymous conserved (PhyloP=0.782 with no splicing effect.

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.112C>A	p.Arg38Arg	synonymous	Exon 3 of 18	NP_061830.3
	SH3BP1	NM_001350055.2		c.112C>A	p.Arg38Arg	synonymous	Exon 3 of 18	NP_001336984.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP1	ENST00000649765.2	MANE Select	c.112C>A	p.Arg38Arg	synonymous	Exon 3 of 18	ENSP00000497104.1	Q9Y3L3-1
	ENSG00000285304	ENST00000451997.6	TSL:2	c.-81C>A		5_prime_UTR	Exon 2 of 17	ENSP00000401076.2
	SH3BP1	ENST00000905665.1		c.112C>A	p.Arg38Arg	synonymous	Exon 3 of 18	ENSP00000575724.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398504 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 689804

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31604

American (AMR) AF: 0.00 AC: 0 AN: 35710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.00 AC: 0 AN: 35748

South Asian (SAS) AF: 0.00 AC: 0 AN: 79240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078964

Other (OTH) AF: 0.00 AC: 0 AN: 57980

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	14
DANN	Benign	0.73
PhyloP100		0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1471015359; hg19: chr22-38037390;