Variant 8-51820436-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_052937.4(PCMTD1):c.989C>G(p.Pro330Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PCMTD1
NM_052937.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.48

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34910372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCMTD1	NM_052937.4 linkuse as main transcript	c.989C>G	p.Pro330Arg	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.989C>G	p.Pro330Arg	missense_variant	6/6	2	NM_052937.4	ENSP00000428099.1	Q96MG8-1
PCMTD1	ENST00000544451.2 linkuse as main transcript	c.761C>G	p.Pro254Arg	missense_variant	4/4	1		ENSP00000444026.1	Q96MG8-2
PCMTD1	ENST00000360540.9 linkuse as main transcript	c.989C>G	p.Pro330Arg	missense_variant	7/7	5		ENSP00000353739.5	Q96MG8-1
PCMTD1	ENST00000519559.1 linkuse as main transcript	n.915C>G		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460458

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726452

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

May 14, 2024

The c.989C>G (p.P330R) 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 989, causing the proline (P) at amino acid position 330 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

0.11

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.085

T;T;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

D;.;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.8

.;L;L

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.2

D;N;N

REVEL

Benign

0.26

Sift

Uncertain

0.019

D;D;D

Sift4G

Uncertain

0.017

D;D;D

Polyphen

0.98

D;P;P

Vest4

0.58

MutPred

0.31

.;Loss of catalytic residue at P329 (P = 0.0168);Loss of catalytic residue at P329 (P = 0.0168);

MVP

0.71

MPC

.;2.6715660745E-4;.

ClinPred

0.67

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.38

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