rs1554573990

Variant names:

• chr8-99832555-C-G
• NM_017890.5:c.9592C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-99832555-C-G
• chr8-99832555-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152564.5(VPS13B):​c.9517C>G​(p.Gln3173Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: VPS13B NM_152564.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.707

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07149851).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13B	NM_017890.5	c.9592C>G	p.Gln3198Glu	missense_variant	Exon 52 of 62	ENST00000358544.7	NP_060360.3
VPS13B	NM_152564.5	c.9517C>G	p.Gln3173Glu	missense_variant	Exon 52 of 62	ENST00000357162.7	NP_689777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000358544.7	c.9592C>G	p.Gln3198Glu	missense_variant	Exon 52 of 62	1	NM_017890.5	ENSP00000351346.2
VPS13B	ENST00000357162.7	c.9517C>G	p.Gln3173Glu	missense_variant	Exon 52 of 62	1	NM_152564.5	ENSP00000349685.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461778 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727166

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.1
DANN	Benign	0.95
DEOGEN2	Benign	0.053	.;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.52	N;N
REVEL	Benign	0.097
Sift	Benign	0.68	T;T
Sift4G	Benign	0.76	T;T
Polyphen		0.0020	B;B
Vest4		0.18
MutPred		0.28		.;Gain of relative solvent accessibility (P = 0.09);
MVP		0.55
MPC		0.13
ClinPred		0.18	T
GERP RS		4.9
Varity_R		0.081
gMVP		0.40

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-100844783;