Genetic Variant NM_030938.5:c.*1098T>C (chr17-59841009-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.270

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
VMP1	NM_030938.5	MANE Select	c.*1098T>C	3_prime_UTR	Exon 12 of 12	NP_112200.2
VMP1	NM_001329395.2		c.*1098T>C	3_prime_UTR	Exon 13 of 13	NP_001316324.1
VMP1	NM_001329394.2		c.*1098T>C	3_prime_UTR	Exon 12 of 12	NP_001316323.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
VMP1	ENST00000262291.9	TSL:1 MANE Select	c.*1098T>C	3_prime_UTR	Exon 12 of 12	ENSP00000262291.3
VMP1	ENST00000585847.6	TSL:2	n.*2000T>C	non_coding_transcript_exon	Exon 11 of 11	ENSP00000465947.1
VMP1	ENST00000586245.6	TSL:4	n.*2048T>C	non_coding_transcript_exon	Exon 11 of 11	ENSP00000466579.1

Frequencies

GnomAD3 genomes

AF:

0.0368

AC:

5604

AN:

152152

Hom.:

372

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00358

AC XY:

AN XY:

16496

show subpopulations

African (AFR)

AF:

0.125

AC:

106

AN:

846

American (AMR)

AF:

0.00616

AC:

AN:

2110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

510

East Asian (EAS)

AF:

0.00

AC:

AN:

1752

South Asian (SAS)

AF:

0.000305

AC:

AN:

6556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

834

Middle Eastern (MID)

AF:

0.0152

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000345

AC:

AN:

14476

Other (OTH)

AF:

0.00646

AC:

AN:

1084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0369

AC:

5625

AN:

152270

Hom.:

375

Cov.:

AF XY:

0.0352

AC XY:

2622

AN XY:

74466

show subpopulations

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:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68030

Other (OTH)

AF:

0.0237

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

233

466

700

933

1166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0186

Hom.:

Bravo

AF:

0.0421

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.8

(source)

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)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over