6-149810956-A-G

Position:

• chr6-149810956-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000464889.7(PCMT1):​c.*378A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 239,334 control chromosomes in the GnomAD database, including 33,770 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 (24835 hom., cov: 32)
  • Exomes 𝑓: 0.43 (8935 hom.)
• Consequence: PCMT1 ENST00000464889.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• 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.*378A>G		3_prime_UTR_variant	8/8	ENST00000464889.7	NP_001347381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCMT1	ENST00000464889.7	c.*378A>G		3_prime_UTR_variant	8/8	1	NM_001360452.2	ENSP00000420813	P4

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80978 AN: 151944 Hom.: 24767 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 0.429 AC: 37468 AN: 87272 Hom.: 8935 Cov.: 0 AF XY: 0.432 AC XY: 19612 AN XY: 45378

Gnomad4 AFR exome AF: 0.806

Gnomad4 AMR exome AF: 0.643

Gnomad4 ASJ exome AF: 0.470

Gnomad4 EAS exome AF: 0.760

Gnomad4 SAS exome AF: 0.504

Gnomad4 FIN exome AF: 0.379

Gnomad4 NFE exome AF: 0.362

Gnomad4 OTH exome AF: 0.455

GnomAD4 genome AF: 0.533 AC: 81107 AN: 152062 Hom.: 24835 Cov.: 32 AF XY: 0.537 AC XY: 39951 AN XY: 74328

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.533

Alfa AF: 0.405 Hom.: 13577

Bravo AF: 0.568

Asia WGS AF: 0.667 AC: 2320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7818; hg19: chr6-150132092;