NM_152464.3:c.16C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152464.3(VMA12):c.16C>T(p.Leu6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,350 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L6V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

VMA12
NM_152464.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.20

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05672899).

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	UniProt
VMA12	NM_152464.3	MANE Select	c.16C>T	p.Leu6Phe	missense	Exon 1 of 6	NP_689677.1	Q8N511
POLDIP2	NM_015584.5	MANE Select	c.-238G>A		upstream_gene	N/A	NP_056399.1	Q9Y2S7
POLDIP2	NM_001290145.2		c.-238G>A		upstream_gene	N/A	NP_001277074.1	B4DEM9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VMA12	ENST00000292114.8	TSL:1 MANE Select	c.16C>T	p.Leu6Phe	missense	Exon 1 of 6	ENSP00000292114.3	Q8N511
VMA12	ENST00000971958.1		c.16C>T	p.Leu6Phe	missense	Exon 1 of 6	ENSP00000642017.1
VMA12	ENST00000555264.6	TSL:5	n.16C>T		non_coding_transcript_exon	Exon 1 of 7	ENSP00000462356.1	J3KS81

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

247250

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000494

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460350

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726494

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

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:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111868

Other (OTH)

AF:

0.0000331

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.5

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0069

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.71

M_CAP

Benign

0.012

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-1.2

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.2

REVEL

Benign

0.026

Sift

Benign

0.12

Sift4G

Benign

0.090

Polyphen

0.12

Vest4

0.15

MutPred

0.23

Loss of MoRF binding (P = 0.1144)

MVP

0.030

MPC

0.27

ClinPred

0.061

GERP RS

-9.5

PromoterAI

-0.091

Neutral

(source)

Varity_R

0.052

gMVP

0.20

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