chr6-149793634-C-A

Variant names:

• chr6-149793634-C-A
• NM_001360452.2:c.383C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001360452.2(PCMT1):​c.383C>A​(p.Pro128Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PCMT1 NM_001360452.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.04
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.383C>A	p.Pro128Gln	missense	Exon 5 of 8	NP_001347381.1	A0A384MDK7
	PCMT1	NM_001252049.1		c.557C>A	p.Pro186Gln	missense	Exon 5 of 8	NP_001238978.1	P22061
	PCMT1	NM_001252053.1		c.557C>A	p.Pro186Gln	missense	Exon 5 of 7	NP_001238982.1	P22061

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCMT1	ENST00000464889.7	TSL:1 MANE Select	c.383C>A	p.Pro128Gln	missense	Exon 5 of 8	ENSP00000420813.2	P22061-1
	PCMT1	ENST00000367384.8	TSL:1	c.383C>A	p.Pro128Gln	missense	Exon 5 of 8	ENSP00000356354.3	P22061-2
	PCMT1	ENST00000367378.6	TSL:1	c.383C>A	p.Pro128Gln	missense	Exon 5 of 7	ENSP00000356348.2	P22061-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1412014 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 702014

African (AFR) AF: 0.00 AC: 0 AN: 29424

American (AMR) AF: 0.00 AC: 0 AN: 32218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24976

East Asian (EAS) AF: 0.00 AC: 0 AN: 35268

South Asian (SAS) AF: 0.00 AC: 0 AN: 76732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096578

Other (OTH) AF: 0.00 AC: 0 AN: 58436

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		6.0
PrimateAI	Uncertain	0.49	T
REVEL	Benign	0.26
Sift4G	Benign	0.20	T
Polyphen		0.12	B
Vest4		0.49
MutPred		0.49		Loss of ubiquitination at K125 (P = 0.1166)
MVP		0.51
MPC		0.90
ClinPred		0.78	D
GERP RS		5.8
Varity_R		0.46
gMVP		0.75
Mutation Taster		=49/51	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr6-150114770;