8-99832530-T-G

Variant names:

• chr8-99832530-T-G
• rs36074608
• NM_017890.5:c.9567T>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_017890.5(VPS13B):​c.9567T>G​(p.Ser3189Ser) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S3189S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: VPS13B NM_017890.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00200
• Publications: 0 publications found

Genes affected

VPS13B (HGNC:2183): (vacuolar protein sorting 13 homolog B) This gene encodes a potential transmembrane protein that may function in vesicle-mediated transport and sorting of proteins within the cell. This protein may play a role in the development and the function of the eye, hematological system, and central nervous system. Mutations in this gene have been associated with Cohen syndrome. Multiple splice variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

VPS13B Gene-Disease associations (from GenCC):

• Cohen syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Laboratory for Molecular Medicine, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-99832530-T-G is Benign according to our data. Variant chr8-99832530-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1581438.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.002 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017890.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13B	NM_017890.5	MANE Plus Clinical	c.9567T>G	p.Ser3189Ser	synonymous	Exon 52 of 62	NP_060360.3
	VPS13B	NM_152564.5	MANE Select	c.9492T>G	p.Ser3164Ser	synonymous	Exon 52 of 62	NP_689777.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13B	ENST00000358544.7	TSL:1 MANE Plus Clinical	c.9567T>G	p.Ser3189Ser	synonymous	Exon 52 of 62	ENSP00000351346.2
	VPS13B	ENST00000357162.7	TSL:1 MANE Select	c.9492T>G	p.Ser3164Ser	synonymous	Exon 52 of 62	ENSP00000349685.2
	VPS13B	ENST00000682153.1		n.9567T>G		non_coding_transcript_exon	Exon 52 of 62	ENSP00000507923.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cohen syndrome Benign:1

Nov 09, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.60
PhyloP100		-0.0020

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs36074608; hg19: chr8-100844758;