6-149754137-T-C

Variant names:

• chr6-149754137-T-C
• rs10782318
• NM_001360452.2:c.55+4181T>C

Variant summary

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

The NM_001360452.2(PCMT1):​c.55+4181T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,080 control chromosomes in the GnomAD database, including 10,587 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 0.34 (10587 hom., cov: 32)
• Consequence: PCMT1 NM_001360452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• Publications: 14 publications found

Genes affected

PCMT1 (HGNC:8728): (protein-L-isoaspartate (D-aspartate) O-methyltransferase) This gene encodes a member of the type II class of protein carboxyl methyltransferase enzymes. The encoded enzyme plays a role in protein repair by recognizing and converting D-aspartyl and L-isoaspartyl residues resulting from spontaneous deamidation back to the normal L-aspartyl form. The encoded protein may play a protective role in the pathogenesis of Alzheimer's disease, and single nucleotide polymorphisms in this gene have been associated with spina bifida and premature ovarian failure. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001360452.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCMT1	NM_001360452.2	MANE Select	c.55+4181T>C		intron	N/A	NP_001347381.1	A0A384MDK7
	PCMT1	NM_001252049.1		c.229+4181T>C		intron	N/A	NP_001238978.1	P22061
	PCMT1	NM_001252053.1		c.229+4181T>C		intron	N/A	NP_001238982.1	P22061

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCMT1	ENST00000464889.7	TSL:1 MANE Select	c.55+4181T>C		intron	N/A	ENSP00000420813.2	P22061-1
	PCMT1	ENST00000367384.8	TSL:1	c.55+4181T>C		intron	N/A	ENSP00000356354.3	P22061-2
	PCMT1	ENST00000367378.6	TSL:1	c.55+4181T>C		intron	N/A	ENSP00000356348.2	P22061-1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52000 AN: 151962 Hom.: 10572 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.342 AC: 52033 AN: 152080 Hom.: 10587 Cov.: 32 AF XY: 0.351 AC XY: 26053 AN XY: 74310

African (AFR) AF: 0.173 AC: 7200 AN: 41540

American (AMR) AF: 0.528 AC: 8059 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1406 AN: 3472

East Asian (EAS) AF: 0.811 AC: 4200 AN: 5178

South Asian (SAS) AF: 0.410 AC: 1977 AN: 4820

European-Finnish (FIN) AF: 0.377 AC: 3973 AN: 10532

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23991 AN: 67964

Other (OTH) AF: 0.374 AC: 791 AN: 2116

Alfa AF: 0.372 Hom.: 5832

Bravo AF: 0.353

Asia WGS AF: 0.561 AC: 1953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.49
PhyloP100		-0.053
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: rs10782318; hg19: chr6-150075273;