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
• Publications: 24 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCMT1	NM_001360452.2	MANE Select	c.*378A>G		3_prime_UTR	Exon 8 of 8	NP_001347381.1
	PCMT1	NM_001252049.1		c.*328A>G		3_prime_UTR	Exon 8 of 8	NP_001238978.1
	PCMT1	NM_005389.2		c.*378A>G		3_prime_UTR	Exon 8 of 8	NP_005380.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCMT1	ENST00000464889.7	TSL:1 MANE Select	c.*378A>G		3_prime_UTR	Exon 8 of 8	ENSP00000420813.2
	PCMT1	ENST00000367384.8	TSL:1	c.*328A>G		3_prime_UTR	Exon 8 of 8	ENSP00000356354.3
	PCMT1	ENST00000367380.9	TSL:2	c.*378A>G		3_prime_UTR	Exon 7 of 7	ENSP00000356350.6

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

African (AFR) AF: 0.806 AC: 2164 AN: 2684

American (AMR) AF: 0.643 AC: 1785 AN: 2774

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1478 AN: 3148

East Asian (EAS) AF: 0.760 AC: 3991 AN: 5252

South Asian (SAS) AF: 0.504 AC: 3003 AN: 5958

European-Finnish (FIN) AF: 0.379 AC: 1685 AN: 4446

Middle Eastern (MID) AF: 0.440 AC: 177 AN: 402

European-Non Finnish (NFE) AF: 0.362 AC: 20560 AN: 56840

Other (OTH) 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

African (AFR) AF: 0.806 AC: 33437 AN: 41508

American (AMR) AF: 0.604 AC: 9216 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1566 AN: 3470

East Asian (EAS) AF: 0.831 AC: 4301 AN: 5176

South Asian (SAS) AF: 0.505 AC: 2435 AN: 4822

European-Finnish (FIN) AF: 0.378 AC: 3993 AN: 10552

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24563 AN: 67948

Other (OTH) AF: 0.533 AC: 1128 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		3.1
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

Other links and lift over

dbSNP: rs7818; hg19: chr6-150132092;