Genetic Variant NM_004738.5:c.-198_-187dupGCCCTCGCCCTC (chr20-58389257-G-GCCTCGCCCTCGC) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_004738.5(VAPB):c.-198_-187dupGCCCTCGCCCTC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 518,638 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

VAPB
NM_004738.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.441

Variant links:

Genes affected

VAPB (HGNC:12649): (VAMP associated protein B and C) The protein encoded by this gene is a type IV membrane protein found in plasma and intracellular vesicle membranes. The encoded protein is found as a homodimer and as a heterodimer with VAPA. This protein also can interact with VAMP1 and VAMP2 and may be involved in vesicle trafficking. [provided by RefSeq, Jul 2008]

VAPB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
VAPB	NM_004738.5 link	c.-198_-187dupGCCCTCGCCCTC	5_prime_UTR_variant	Exon 1 of 6	ENST00000475243.6	NP_004729.1	O95292-1Q53XM7
VAPB	NM_001195677.2 link	c.-198_-187dupGCCCTCGCCCTC	5_prime_UTR_variant	Exon 1 of 3		NP_001182606.1	O95292-2
VAPB	NR_036633.2 link	n.34_45dupGCCCTCGCCCTC	non_coding_transcript_exon_variant	Exon 1 of 4
VAPB	XR_001754433.3 link	n.34_45dupGCCCTCGCCCTC	non_coding_transcript_exon_variant	Exon 1 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
VAPB	ENST00000475243 link	c.-198_-187dupGCCCTCGCCCTC	5_prime_UTR_variant	Exon 1 of 6	1	NM_004738.5	ENSP00000417175.1	O95292-1
VAPB	ENST00000395802.7 link	c.-203_-202insCCTCGCCCTCGC	upstream_gene_variant		1		ENSP00000379147.3	O95292-2
VAPB	ENST00000265619.6 link	n.-118_-117insCCTCGCCCTCGC	upstream_gene_variant		2
VAPB	ENST00000520497.1 link	n.-203_-202insCCTCGCCCTCGC	upstream_gene_variant		2		ENSP00000430426.1	E5RK64

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000193

AC:

AN:

518638

Hom.:

Cov.:

AF XY:

0.00000355

AC XY:

AN XY:

281988

show subpopulations

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:

0.00

Gnomad4 OTH exome

AF:

0.0000354

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over