Variant 8-51820457-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052937.4(PCMTD1):c.968C>G(p.Ala323Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000725 in 1,613,758 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 1 hom. )

Consequence

PCMTD1
NM_052937.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

Variant links:

Genes affected

PCMTD1 (HGNC:30483): (protein-L-isoaspartate (D-aspartate) O-methyltransferase domain containing 1) Predicted to enable protein-L-isoaspartate (D-aspartate) O-methyltransferase activity. Predicted to be involved in protein methylation. Predicted to be located in membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PCMTD1 links:

PCMTD1 (HGNC:):

PCMTD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.005237192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCMTD1	NM_052937.4 linkuse as main transcript	c.968C>G	p.Ala323Gly	missense_variant	6/6	ENST00000522514.6	NP_443169.2	Q96MG8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PCMTD1	ENST00000522514.6 linkuse as main transcript	c.968C>G	p.Ala323Gly	missense_variant	6/6	2	NM_052937.4	ENSP00000428099.1	Q96MG8-1
PCMTD1	ENST00000544451.2 linkuse as main transcript	c.740C>G	p.Ala247Gly	missense_variant	4/4	1		ENSP00000444026.1	Q96MG8-2
PCMTD1	ENST00000360540.9 linkuse as main transcript	c.968C>G	p.Ala323Gly	missense_variant	7/7	5		ENSP00000353739.5	Q96MG8-1
PCMTD1	ENST00000519559.1 linkuse as main transcript	n.894C>G		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000996

AC:

AN:

250892

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1461508

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000460

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000101

Hom.:

Bravo

AF:

0.000438

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000453

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.968C>G (p.A323G) alteration is located in exon 6 (coding exon 5) of the PCMTD1 gene. This alteration results from a C to G substitution at nucleotide position 968, causing the alanine (A) at amino acid position 323 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.020

T;T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.034

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.78

T;.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.0052

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

.;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.087

T;T;T

Sift4G

Benign

0.41

T;T;T

Polyphen

0.42

B;B;B

Vest4

0.069

MVP

0.51

MPC

.;2.6715660745E-4;.

ClinPred

0.048

GERP RS

6.0

Varity_R

0.099

gMVP

0.26

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over