Genetic Variant NM_030938.5:c.*1759A>T (chr17-59841670-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.165

Variant links:

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]

VMP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 link	c.*1759A>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000262291.9	NP_112200.2	Q96GC9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VMP1	ENST00000262291.9 link	c.*1759A>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_030938.5	ENSP00000262291.3		Q96GC9-1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28165

AN:

151996

Hom.:

3204

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.212

AC XY:

212

AN XY:

998

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.0515

Gnomad4 ASJ exome

AF:

0.143

Gnomad4 EAS exome

AF:

0.450

Gnomad4 SAS exome

AF:

0.334

Gnomad4 FIN exome

AF:

0.100

Gnomad4 NFE exome

AF:

0.157

Gnomad4 OTH exome

AF:

0.269

GnomAD4 genome

AF:

0.185

AC:

28182

AN:

152114

Hom.:

3214

Cov.:

AF XY:

0.189

AC XY:

14087

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0829

Gnomad4 AMR

AF:

0.173

Gnomad4 ASJ

AF:

0.199

Gnomad4 EAS

AF:

0.438

Gnomad4 SAS

AF:

0.409

Gnomad4 FIN

AF:

0.211

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.202

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

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over