rs199872639

Positions:

• chr8-99481716-A-C
• chr8-99481716-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017890.5(VPS13B):​c.3784A>C​(p.Thr1262Pro) variant causes a missense 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. 15/21 in silico tools predict 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: 32)
• Consequence: VPS13B NM_017890.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026915371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13B	NM_017890.5	c.3784A>C	p.Thr1262Pro	missense_variant	25/62	ENST00000358544.7	NP_060360.3
VPS13B	NM_152564.5	c.3784A>C	p.Thr1262Pro	missense_variant	25/62	ENST00000357162.7	NP_689777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000358544.7	c.3784A>C	p.Thr1262Pro	missense_variant	25/62	1	NM_017890.5	ENSP00000351346
VPS13B	ENST00000357162.7	c.3784A>C	p.Thr1262Pro	missense_variant	25/62	1	NM_152564.5	ENSP00000349685	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.2
DANN	Benign	0.34
DEOGEN2	Benign	0.071	.;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.40	T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.027	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.052
Sift	Benign	0.071	T;T
Sift4G	Benign	0.10	T;T
Polyphen		0.18	B;B
Vest4		0.077
MutPred		0.11		Loss of glycosylation at T1262 (P = 0.0262);Loss of glycosylation at T1262 (P = 0.0262);
MVP		0.16
MPC		0.17
ClinPred		0.15	T
GERP RS		-5.0
Varity_R		0.10
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr8-100493944;