8-51844533-G-A

Variant names:

• chr8-51844533-G-A
• rs10504130
• NM_052937.4:c.410+1128C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052937.4(PCMTD1):​c.410+1128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,082 control chromosomes in the GnomAD database, including 1,292 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 0.12 (1292 hom., cov: 32)
• Consequence: PCMTD1 NM_052937.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCMTD1	NM_052937.4	c.410+1128C>T		intron_variant	Intron 3 of 5	ENST00000522514.6	NP_443169.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCMTD1	ENST00000522514.6	c.410+1128C>T		intron_variant	Intron 3 of 5	2	NM_052937.4	ENSP00000428099.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17856 AN: 151964 Hom.: 1286 Cov.: 32

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0864

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.118 AC: 17881 AN: 152082 Hom.: 1292 Cov.: 32 AF XY: 0.124 AC XY: 9240 AN XY: 74314

African (AFR) AF: 0.0546 AC: 2267 AN: 41500

American (AMR) AF: 0.0863 AC: 1317 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3468

East Asian (EAS) AF: 0.166 AC: 856 AN: 5170

South Asian (SAS) AF: 0.131 AC: 631 AN: 4826

European-Finnish (FIN) AF: 0.238 AC: 2510 AN: 10542

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9433 AN: 67992

Other (OTH) AF: 0.127 AC: 267 AN: 2110

Alfa AF: 0.130 Hom.: 5763

Bravo AF: 0.102

Asia WGS AF: 0.175 AC: 608 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	1.7
DANN	Benign	0.52
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10504130; hg19: chr8-52757093;