Variant rs4816 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001360452.2(PCMT1):c.358G>A(p.Val120Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,563,820 control chromosomes in the GnomAD database, including 143,604 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.53 ( 24834 hom., cov: 33)

Exomes 𝑓: 0.39 ( 118770 hom. )

Consequence

PCMT1
NM_001360452.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.07

Variant links:

Genes affected

PCMT1 (HGNC:8728): (protein-L-isoaspartate (D-aspartate) O-methyltransferase) This gene encodes a member of the type II class of protein carboxyl methyltransferase enzymes. The encoded enzyme plays a role in protein repair by recognizing and converting D-aspartyl and L-isoaspartyl residues resulting from spontaneous deamidation back to the normal L-aspartyl form. The encoded protein may play a protective role in the pathogenesis of Alzheimer's disease, and single nucleotide polymorphisms in this gene have been associated with spina bifida and premature ovarian failure. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

PCMT1 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 (MetaRNN=6.7449474E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCMT1	NM_001360452.2 linkuse as main transcript	c.358G>A	p.Val120Ile	missense_variant	5/8	ENST00000464889.7	NP_001347381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCMT1	ENST00000464889.7 linkuse as main transcript	c.358G>A	p.Val120Ile	missense_variant	5/8	1	NM_001360452.2	ENSP00000420813.2		P22061-1

Frequencies

GnomAD3 genomes

AF:

0.533

AC:

81009

AN:

151940

Hom.:

24766

Cov.:

show subpopulations

Gnomad AFR

AF:

0.805

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.602

Gnomad ASJ

AF:

0.451

Gnomad EAS

AF:

0.829

Gnomad SAS

AF:

0.502

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.529

GnomAD3 exomes

AF:

0.464

AC:

99400

AN:

214124

Hom.:

26182

AF XY:

0.451

AC XY:

52929

AN XY:

117474

show subpopulations

Gnomad AFR exome

AF:

0.807

Gnomad AMR exome

AF:

0.666

Gnomad ASJ exome

AF:

0.439

Gnomad EAS exome

AF:

0.812

Gnomad SAS exome

AF:

0.461

Gnomad FIN exome

AF:

0.381

Gnomad NFE exome

AF:

0.353

Gnomad OTH exome

AF:

0.443

GnomAD4 exome

AF:

0.394

AC:

556834

AN:

1411762

Hom.:

118770

Cov.:

AF XY:

0.396

AC XY:

277540

AN XY:

701586

show subpopulations

Gnomad4 AFR exome

AF:

0.816

Gnomad4 AMR exome

AF:

0.661

Gnomad4 ASJ exome

AF:

0.447

Gnomad4 EAS exome

AF:

0.770

Gnomad4 SAS exome

AF:

0.473

Gnomad4 FIN exome

AF:

0.379

Gnomad4 NFE exome

AF:

0.354

Gnomad4 OTH exome

AF:

0.441

GnomAD4 genome

AF:

0.534

AC:

81138

AN:

152058

Hom.:

24834

Cov.:

AF XY:

0.538

AC XY:

39959

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.805

Gnomad4 AMR

AF:

0.603

Gnomad4 ASJ

AF:

0.451

Gnomad4 EAS

AF:

0.830

Gnomad4 SAS

AF:

0.501

Gnomad4 FIN

AF:

0.378

Gnomad4 NFE

AF:

0.362

Gnomad4 OTH

AF:

0.534

Alfa

AF:

0.404

Hom.:

19519

Bravo

AF:

0.568

TwinsUK

AF:

0.358

AC:

1329

ALSPAC

AF:

0.353

AC:

1362

ESP6500AA

AF:

0.796

AC:

3507

ESP6500EA

AF:

0.373

AC:

3210

ExAC

AF:

0.491

AC:

59638

Asia WGS

AF:

0.665

AC:

2308

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.8

DANN

Benign

0.86

DEOGEN2

Benign

0.061

.;T;T;T;.;T;.;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.67

T;.;T;T;T;T;T;T

MetaRNN

Benign

6.7e-7

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.96

N;N;N;.;.;.;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.16

.;.;.;.;.;.;.;N

REVEL

Benign

0.11

Sift

Benign

0.94

.;.;.;.;.;.;.;T

Sift4G

Benign

0.58

.;.;.;.;T;T;.;T

Polyphen

0.0

B;B;B;.;.;.;.;.

Vest4

0.086, 0.11

MPC

0.65

ClinPred

0.0074

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.42

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

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