rs3851812

Variant names:

• chr17-59841009-T-C
• rs3851812
• NM_030938.5:c.*1098T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030938.5(VMP1):​c.*1098T>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 0.0319 in 180,504 control chromosomes in the GnomAD database, including 384 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 0.037 (375 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (9 hom.)
• Consequence: VMP1 NM_030938.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMP1	NM_030938.5	c.*1098T>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000262291.9	NP_112200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VMP1	ENST00000262291.9	c.*1098T>C		3_prime_UTR_variant	Exon 12 of 12	1	NM_030938.5	ENSP00000262291.3

Frequencies

GnomAD3 genomes AF: 0.0368 AC: 5604 AN: 152152 Hom.: 372 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0240

GnomAD4 exome AF: 0.00475 AC: 134 AN: 28234 Hom.: 9 Cov.: 0 AF XY: 0.00358 AC XY: 59 AN XY: 16496

African (AFR) AF: 0.125 AC: 106 AN: 846

American (AMR) AF: 0.00616 AC: 13 AN: 2110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 510

East Asian (EAS) AF: 0.00 AC: 0 AN: 1752

South Asian (SAS) AF: 0.000305 AC: 2 AN: 6556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 834

Middle Eastern (MID) AF: 0.0152 AC: 1 AN: 66

European-Non Finnish (NFE) AF: 0.000345 AC: 5 AN: 14476

Other (OTH) AF: 0.00646 AC: 7 AN: 1084

GnomAD4 genome AF: 0.0369 AC: 5625 AN: 152270 Hom.: 375 Cov.: 32 AF XY: 0.0352 AC XY: 2622 AN XY: 74466

African (AFR) AF: 0.129 AC: 5357 AN: 41530

American (AMR) AF: 0.0117 AC: 179 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68030

Other (OTH) AF: 0.0237 AC: 50 AN: 2108

Alfa AF: 0.0186 Hom.: 54

Bravo AF: 0.0421

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.8
DANN	Benign	0.72
PhyloP100		0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3851812; hg19: chr17-57918370;