17-28357690-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PM2PM5BP4_Strong

The NM_152464.3(VMA12):c.20C>G(p.Ala7Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A7V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

VMA12
NM_152464.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.326

Publications

3 publications found

Variant links:

Genes affected

VMA12 (HGNC:18085): (transmembrane protein 199) The protein encoded by this gene has been observed to localize to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) and coat protein complex I (COPI) in some human cells. The encoded protein shares some homology with the yeast protein Vma12. Defects in this gene are a cause of congenital disorder of glycosylation, type IIp. [provided by RefSeq, Mar 2016]

VMA12 links:

ENSG00000258924 (HGNC:):

ENSG00000258924 links:

POLDIP2 (HGNC:23781): (DNA polymerase delta interacting protein 2) This gene encodes a protein that interacts with the DNA polymerase delta p50 subunit, as well as with proliferating cell nuclear antigen. The encoded protein maybe play a role in the ability of the replication fork to bypass DNA lesions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

POLDIP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr17-28357690-C-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 218965.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.05862707).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152464.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
VMA12	NM_152464.3	MANE Select	c.20C>G	p.Ala7Gly	missense	Exon 1 of 6	NP_689677.1
POLDIP2	NM_015584.5	MANE Select	c.-242G>C		upstream_gene	N/A	NP_056399.1
POLDIP2	NM_001290145.2		c.-242G>C		upstream_gene	N/A	NP_001277074.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
VMA12	ENST00000292114.8	TSL:1 MANE Select	c.20C>G	p.Ala7Gly	missense	Exon 1 of 6	ENSP00000292114.3
VMA12	ENST00000971958.1		c.20C>G	p.Ala7Gly	missense	Exon 1 of 6	ENSP00000642017.1
VMA12	ENST00000555264.6	TSL:5	n.20C>G		non_coding_transcript_exon	Exon 1 of 7	ENSP00000462356.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000404

AC:

AN:

247246

AF XY:

0.00000745

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460336

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726506

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.0000224

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111870

Other (OTH)

AF:

0.00

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.0089

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.60

M_CAP

Benign

0.021

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

0.33

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.3

REVEL

Benign

0.049

Sift

Benign

0.17

Sift4G

Uncertain

0.012

Polyphen

0.0010

Vest4

0.17

MutPred

0.23

Gain of relative solvent accessibility (P = 0.0082)

MVP

0.10

MPC

0.23

ClinPred

0.52

GERP RS

1.7

PromoterAI

-0.097

Neutral

(source)

Varity_R

0.055

gMVP

0.45

Mutation Taster

=55/45

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over