17-59755030-T-G

Variant names:

• chr17-59755030-T-G
• rs2777899
• NM_030938.5:c.415-9941T>G

Variant summary

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

The NM_030938.5(VMP1):​c.415-9941T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 142,236 control chromosomes in the GnomAD database, including 14,323 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 0.43 (14323 hom., cov: 22)
• Consequence: VMP1 NM_030938.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 12 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030938.5. 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
	VMP1	NM_030938.5	MANE Select	c.415-9941T>G		intron	N/A	NP_112200.2
	VMP1	NM_001329395.2		c.415-9941T>G		intron	N/A	NP_001316324.1	K7EPE7
	VMP1	NM_001329394.2		c.415-9941T>G		intron	N/A	NP_001316323.1	Q96GC9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VMP1	ENST00000262291.9	TSL:1 MANE Select	c.415-9941T>G		intron	N/A	ENSP00000262291.3	Q96GC9-1
	VMP1	ENST00000591877.2	TSL:3	c.415-9941T>G		intron	N/A	ENSP00000467350.2	K7EPE7
	VMP1	ENST00000891501.1		c.415-9941T>G		intron	N/A	ENSP00000561560.1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 60739 AN: 142138 Hom.: 14324 Cov.: 22

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.374

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.426

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.427 AC: 60744 AN: 142236 Hom.: 14323 Cov.: 22 AF XY: 0.426 AC XY: 29282 AN XY: 68782

African (AFR) AF: 0.185 AC: 6987 AN: 37666

American (AMR) AF: 0.470 AC: 6450 AN: 13734

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1841 AN: 3442

East Asian (EAS) AF: 0.438 AC: 1996 AN: 4554

South Asian (SAS) AF: 0.464 AC: 2041 AN: 4394

European-Finnish (FIN) AF: 0.507 AC: 4470 AN: 8824

Middle Eastern (MID) AF: 0.365 AC: 97 AN: 266

European-Non Finnish (NFE) AF: 0.536 AC: 35620 AN: 66504

Other (OTH) AF: 0.421 AC: 823 AN: 1956

Alfa AF: 0.480 Hom.: 8596

Bravo AF: 0.405

Asia WGS AF: 0.370 AC: 1284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.4
DANN	Benign	0.61
PhyloP100		0.015
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: rs2777899; hg19: chr17-57832391;