rs1292037

chr17-59841547-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030938.5(VMP1):c.*1636T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 207,612 control chromosomes in the GnomAD database, including 5,544 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3209 hom., cov: 32)
  • Exomes 𝑓: 0.26 (2335 hom.)
• Consequence: VMP1 NM_030938.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372

Genes affected

VMP1 (HGNC:29559): (vacuole membrane protein 1) This gene encodes a transmembrane protein that plays a key regulatory role in the process of autophagy. The ectopic overexpression of the encoded protein in cultured cells triggers autophagy even under nutrient-rich conditions. This gene is overexpressed in pancreatitis affected acinar cells where the encoded protein mediates sequestration and degradation of potentially deleterious activated zymogen granules in a process termed, zymophagy. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VMP1	NM_030938.5	c.*1636T>C		3_prime_UTR_variant	12/12	ENST00000262291.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VMP1	ENST00000262291.9	c.*1636T>C		3_prime_UTR_variant	12/12	1	NM_030938.5	P1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28121 AN: 151942 Hom.: 3199 Cov.: 32

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.260 AC: 14456 AN: 55552 Hom.: 2335 Cov.: 0 AF XY: 0.280 AC XY: 8759 AN XY: 31278

Gnomad4 AFR exome AF: 0.0695

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.449

Gnomad4 SAS exome AF: 0.423

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.185 AC: 28137 AN: 152060 Hom.: 3209 Cov.: 32 AF XY: 0.189 AC XY: 14070 AN XY: 74338

Gnomad4 AFR AF: 0.0826

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.202

Alfa AF: 0.189 Hom.: 450

Bravo AF: 0.171

Asia WGS AF: 0.420 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	10
Dann	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1292037; hg19: chr17-57918908;