chr20-58389483-G-A

Position:

• chr20-58389483-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_004738.5(VAPB):​c.24G>A​(p.Leu8=) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VAPB NM_004738.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.23

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 20-58389483-G-A is Benign according to our data. Variant chr20-58389483-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2935194.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.23 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAPB	NM_004738.5	c.24G>A	p.Leu8=	synonymous_variant	1/6	ENST00000475243.6
VAPB	NM_001195677.2	c.24G>A	p.Leu8=	synonymous_variant	1/3
VAPB	NR_036633.2	n.255G>A		non_coding_transcript_exon_variant	1/4
VAPB	XR_001754433.3	n.255G>A		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAPB	ENST00000475243.6	c.24G>A	p.Leu8=	synonymous_variant	1/6	1	NM_004738.5	P1
VAPB	ENST00000395802.7	c.24G>A	p.Leu8=	synonymous_variant	1/3	1
VAPB	ENST00000265619.6	n.109G>A		non_coding_transcript_exon_variant	1/6	2
VAPB	ENST00000520497.1	c.24G>A	p.Leu8=	synonymous_variant, NMD_transcript_variant	1/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Amyotrophic lateral sclerosis type 8;C1854058:Adult-onset proximal spinal muscular atrophy, autosomal dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.96

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: chr20-56964539;