chr6-149809506-C-T

Position:

• chr6-149809506-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCMT1	NM_001360452.2	c.*38-1110C>T		intron_variant		ENST00000464889.7	NP_001347381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCMT1	ENST00000464889.7	c.*38-1110C>T		intron_variant		1	NM_001360452.2	ENSP00000420813.2

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

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.533

Alfa AF: 0.407 Hom.: 13383

Bravo AF: 0.564

Asia WGS AF: 0.665 AC: 2301 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2151913; hg19: chr6-150130642;