17-59841670-A-T

Variant names:

• chr17-59841670-A-T
• rs13137
• NM_030938.5:c.*1759A>T

Variant summary

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

The NM_030938.5(VMP1):​c.*1759A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 153,774 control chromosomes in the GnomAD database, including 3,269 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 (3214 hom., cov: 32)
  • Exomes 𝑓: 0.19 (55 hom.)
• Consequence: VMP1 NM_030938.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• Publications: 17 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=-0.83).
• 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 rank	MANE	Protein	UniProt
VMP1	NM_030938.5	c.*1759A>T		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.*1759A>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_030938.5	ENSP00000262291.3

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28165 AN: 151996 Hom.: 3204 Cov.: 32

Gnomad AFR AF: 0.0831

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.194 AC: 322 AN: 1660 Hom.: 55 Cov.: 0 AF XY: 0.212 AC XY: 212 AN XY: 998

African (AFR) AF: 0.125 AC: 4 AN: 32

American (AMR) AF: 0.0515 AC: 10 AN: 194

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 4 AN: 28

East Asian (EAS) AF: 0.450 AC: 27 AN: 60

South Asian (SAS) AF: 0.334 AC: 117 AN: 350

European-Finnish (FIN) AF: 0.100 AC: 4 AN: 40

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.157 AC: 142 AN: 902

Other (OTH) AF: 0.269 AC: 14 AN: 52

GnomAD4 genome AF: 0.185 AC: 28182 AN: 152114 Hom.: 3214 Cov.: 32 AF XY: 0.189 AC XY: 14087 AN XY: 74338

African (AFR) AF: 0.0829 AC: 3443 AN: 41512

American (AMR) AF: 0.173 AC: 2638 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3468

East Asian (EAS) AF: 0.438 AC: 2265 AN: 5170

South Asian (SAS) AF: 0.409 AC: 1977 AN: 4828

European-Finnish (FIN) AF: 0.211 AC: 2225 AN: 10552

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14268 AN: 67984

Other (OTH) AF: 0.202 AC: 426 AN: 2114

Alfa AF: 0.191 Hom.: 398

Bravo AF: 0.171

Asia WGS AF: 0.420 AC: 1458 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.8
DANN	Benign	0.59
PhyloP100		0.17

Splicing

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

Other links and lift over

dbSNP: rs13137; hg19: chr17-57919031;