NM_001360452.2:c.358G>C

Variant names:

• chr6-149793609-G-C
• rs4816
• NM_001360452.2:c.358G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001360452.2(PCMT1):​c.358G>C​(p.Val120Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PCMT1 NM_001360452.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07
• Publications: 61 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15926251).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCMT1	NM_001360452.2	c.358G>C	p.Val120Leu	missense_variant	Exon 5 of 8	ENST00000464889.7	NP_001347381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCMT1	ENST00000464889.7	c.358G>C	p.Val120Leu	missense_variant	Exon 5 of 8	1	NM_001360452.2	ENSP00000420813.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.064	.;T;T;T;.;T;.;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	D;.;D;D;D;D;D;D
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.15	N;N;N;.;.;.;.;.
PhyloP100		2.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.56	.;.;.;.;.;.;.;N
REVEL	Benign	0.12
Sift	Benign	0.44	.;.;.;.;.;.;.;T
Sift4G	Benign	0.39	.;.;.;.;T;T;.;T
Polyphen		0.0	B;B;B;.;.;.;.;.
Vest4		0.18, 0.20
MutPred		0.52		Loss of ubiquitination at K125 (P = 0.1166);Loss of ubiquitination at K125 (P = 0.1166);Loss of ubiquitination at K125 (P = 0.1166);.;.;.;.;.;
MVP		0.17
MPC		0.79
ClinPred		0.53	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.67
Mutation Taster		=98/2	polymorphism

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

dbSNP: rs4816; hg19: chr6-150114745;