chr6-149810956-A-G

Variant names:

• chr6-149810956-A-G
• rs7818
• NM_001360452.2:c.*378A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001360452.2(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 NM_001360452.2 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]

ENSG00000285889 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PCMT1	NM_001360452.2	c.*378A>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000464889.7	NP_001347381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCMT1	ENST00000464889.7	c.*378A>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_001360452.2	ENSP00000420813.2

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 AC: 2164 AN: 2684

Gnomad4 AMR exome AF: 0.643 AC: 1785 AN: 2774

Gnomad4 ASJ exome AF: 0.470 AC: 1478 AN: 3148

Gnomad4 EAS exome AF: 0.760 AC: 3991 AN: 5252

Gnomad4 SAS exome AF: 0.504 AC: 3003 AN: 5958

Gnomad4 FIN exome AF: 0.379 AC: 1685 AN: 4446

Gnomad4 NFE exome AF: 0.362 AC: 20560 AN: 56840

Gnomad4 Remaining exome AF: 0.455 AC: 2625 AN: 5768

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 AC: 0.805556 AN: 0.805556

Gnomad4 AMR AF: 0.604 AC: 0.603615 AN: 0.603615

Gnomad4 ASJ AF: 0.451 AC: 0.451297 AN: 0.451297

Gnomad4 EAS AF: 0.831 AC: 0.830951 AN: 0.830951

Gnomad4 SAS AF: 0.505 AC: 0.504977 AN: 0.504977

Gnomad4 FIN AF: 0.378 AC: 0.378412 AN: 0.378412

Gnomad4 NFE AF: 0.361 AC: 0.361497 AN: 0.361497

Gnomad4 OTH AF: 0.533 AC: 0.533081 AN: 0.533081

Alfa AF: 0.428 Hom.: 20267

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
Mutation Taster		=100/0	polymorphism (auto)

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;