NM_001360452.2:c.*38-1110C>T

Variant names:

• chr6-149809506-C-T
• rs2151913
• NM_001360452.2:c.*38-1110C>T

Variant summary

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

The NM_001360452.2(PCMT1):​c.*38-1110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,796 control chromosomes in the GnomAD database, including 24,409 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 0.53 (24409 hom., cov: 32)
• Consequence: PCMT1 NM_001360452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805
• Publications: 15 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]

ENSG00000285889 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 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.*38-1110C>T		intron	N/A	NP_001347381.1
	PCMT1	NM_001252049.1		c.849-1110C>T		intron	N/A	NP_001238978.1
	PCMT1	NM_005389.2		c.*38-1110C>T		intron	N/A	NP_005380.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCMT1	ENST00000464889.7	TSL:1 MANE Select	c.*38-1110C>T		intron	N/A	ENSP00000420813.2
	PCMT1	ENST00000367384.8	TSL:1	c.675-1110C>T		intron	N/A	ENSP00000356354.3
	PCMT1	ENST00000863139.1		c.*38-1110C>T		intron	N/A	ENSP00000533198.1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80380 AN: 151678 Hom.: 24347 Cov.: 32

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.530 AC: 80503 AN: 151796 Hom.: 24409 Cov.: 32 AF XY: 0.535 AC XY: 39674 AN XY: 74174

African (AFR) AF: 0.794 AC: 32909 AN: 41422

American (AMR) AF: 0.603 AC: 9190 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1564 AN: 3464

East Asian (EAS) AF: 0.831 AC: 4299 AN: 5176

South Asian (SAS) AF: 0.505 AC: 2429 AN: 4806

European-Finnish (FIN) AF: 0.378 AC: 3955 AN: 10452

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24563 AN: 67912

Other (OTH) AF: 0.533 AC: 1125 AN: 2110

Alfa AF: 0.415 Hom.: 16802

Bravo AF: 0.564

Asia WGS AF: 0.665 AC: 2301 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.39
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2151913; hg19: chr6-150130642;