Variant 8-51820616-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052937.4(PCMTD1):c.809A>G(p.Gln270Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,611,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PCMTD1
NM_052937.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09970716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCMTD1	NM_052937.4 linkuse as main transcript	c.809A>G	p.Gln270Arg	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.809A>G	p.Gln270Arg	missense_variant	6/6	2	NM_052937.4	ENSP00000428099.1	Q96MG8-1
PCMTD1	ENST00000544451.2 linkuse as main transcript	c.581A>G	p.Gln194Arg	missense_variant	4/4	1		ENSP00000444026.1	Q96MG8-2
PCMTD1	ENST00000360540.9 linkuse as main transcript	c.809A>G	p.Gln270Arg	missense_variant	7/7	5		ENSP00000353739.5	Q96MG8-1
PCMTD1	ENST00000519559.1 linkuse as main transcript	n.735A>G		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251150

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1459424

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

725852

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000159

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

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

Oct 29, 2024

The c.809A>G (p.Q270R) alteration is located in exon 6 (coding exon 5) of the PCMTD1 gene. This alteration results from a A to G substitution at nucleotide position 809, causing the glutamine (Q) at amino acid position 270 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0080

T;T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.86

D;.;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

.;L;L

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.23

N;N;N

REVEL

Benign

0.048

Sift

Benign

0.35

T;T;T

Sift4G

Benign

0.90

T;T;T

Polyphen

0.88

P;B;B

Vest4

0.26

MutPred

0.30

.;Gain of MoRF binding (P = 0.0277);Gain of MoRF binding (P = 0.0277);

MVP

0.43

MPC

1.2

ClinPred

0.14

GERP RS

3.4

Varity_R

0.084

gMVP

0.40

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