chr20-58389257-G-GCCTCGCCCTCGC

Variant names:

• chr20-58389257-G-GCCTCGCCCTCGC
• rs765965868
• NM_004738.5:c.-198_-187dupGCCCTCGCCCTC

Variant summary

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

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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis type 8

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
• adult-onset proximal spinal muscular atrophy, autosomal dominant

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004738.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAPB	NM_004738.5	MANE Select	c.-198_-187dupGCCCTCGCCCTC		5_prime_UTR	Exon 1 of 6	NP_004729.1	O95292-1
	VAPB	NM_001195677.2		c.-198_-187dupGCCCTCGCCCTC		5_prime_UTR	Exon 1 of 3	NP_001182606.1	O95292-2
	VAPB	NR_036633.2		n.34_45dupGCCCTCGCCCTC		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAPB	ENST00000475243.6	TSL:1 MANE Select	c.-198_-187dupGCCCTCGCCCTC		5_prime_UTR	Exon 1 of 6	ENSP00000417175.1	O95292-1
	VAPB	ENST00000903510.1		c.-198_-187dupGCCCTCGCCCTC		5_prime_UTR	Exon 1 of 7	ENSP00000573569.1
	VAPB	ENST00000903509.1		c.-198_-187dupGCCCTCGCCCTC		5_prime_UTR	Exon 1 of 5	ENSP00000573568.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000193 AC: 1 AN: 518638 Hom.: 0 Cov.: 5 AF XY: 0.00000355 AC XY: 1 AN XY: 281988

African (AFR) AF: 0.00 AC: 0 AN: 12532

American (AMR) AF: 0.00 AC: 0 AN: 32480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18724

East Asian (EAS) AF: 0.00 AC: 0 AN: 29448

South Asian (SAS) AF: 0.00 AC: 0 AN: 60338

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2330

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 302486

Other (OTH) AF: 0.0000354 AC: 1 AN: 28232

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.44

Splicing

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

Other links and lift over

dbSNP: rs765965868; hg19: chr20-56964313;