rs1013621

Positions:

• chr8-51888831-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052937.4(PCMTD1):​c.-96+10099G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,024 control chromosomes in the GnomAD database, including 23,690 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (23690 hom., cov: 32)
• Consequence: PCMTD1 NM_052937.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCMTD1	NM_052937.4	c.-96+10099G>A		intron_variant		ENST00000522514.6	NP_443169.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCMTD1	ENST00000522514.6	c.-96+10099G>A		intron_variant		2	NM_052937.4	ENSP00000428099	P1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77169 AN: 151906 Hom.: 23703 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.538

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.508 AC: 77155 AN: 152024 Hom.: 23690 Cov.: 32 AF XY: 0.505 AC XY: 37554 AN XY: 74294

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.533

Alfa AF: 0.617 Hom.: 15879

Bravo AF: 0.497

Asia WGS AF: 0.494 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs1013621; hg19: chr8-52801391;