rs386834070

Variant names:

• chr8-99134644-C-A
• rs386834070
• NM_017890.5:c.1219C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-99134644-C-A
• chr8-99134644-C-T

Variant summary

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

The NM_017890.5(VPS13B):​c.1219C>A​(p.Gln407Lys) variant causes a missense change. 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. Q407H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VPS13B NM_017890.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.26
• Publications: 4 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: Uncertain_significance. The variant received 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
VPS13B	NM_017890.5	c.1219C>A	p.Gln407Lys	missense_variant	Exon 9 of 62	ENST00000358544.7	NP_060360.3
VPS13B	NM_152564.5	c.1219C>A	p.Gln407Lys	missense_variant	Exon 9 of 62	ENST00000357162.7	NP_689777.3
VPS13B	NM_015243.3	c.1219C>A	p.Gln407Lys	missense_variant	Exon 9 of 18		NP_056058.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000358544.7	c.1219C>A	p.Gln407Lys	missense_variant	Exon 9 of 62	1	NM_017890.5	ENSP00000351346.2
VPS13B	ENST00000357162.7	c.1219C>A	p.Gln407Lys	missense_variant	Exon 9 of 62	1	NM_152564.5	ENSP00000349685.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.088	.;.;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.3	M;M;M
PhyloP100		5.3
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.46	T;T;T
Sift4G	Uncertain	0.054	T;T;T
Polyphen		0.79	P;D;D
Vest4		0.65
MutPred		0.38		Gain of ubiquitination at Q407 (P = 0.0121);Gain of ubiquitination at Q407 (P = 0.0121);Gain of ubiquitination at Q407 (P = 0.0121);
MVP		0.80
MPC		0.27
ClinPred		0.85	D
GERP RS		5.3
Varity_R		0.43
gMVP		0.45
Mutation Taster		=60/40	polymorphism

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

Other links and lift over

dbSNP: rs386834070; hg19: chr8-100146872;