NM_001360452.2:c.-107C>A

Variant names:

• chr6-149749795-C-A
• rs564771067
• NM_001360452.2:c.-107C>A

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.-107C>A variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PCMT1 NM_001360452.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• 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]

NUP43 (HGNC:21182): (nucleoporin 43) Bidirectional transport of macromolecules between the cytoplasm and nucleus occurs through nuclear pore complexes (NPCs) embedded in the nuclear envelope. NPCs are composed of subcomplexes, and NUP43 is part of one such subcomplex, Nup107-160 (Loiodice et al., 2004 [PubMed 15146057]).[supplied by OMIM, Mar 2008]

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=0.12924165).

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.-107C>A		5_prime_UTR	Exon 1 of 8	NP_001347381.1	A0A384MDK7
	PCMT1	NM_001252049.1		c.68C>A	p.Ala23Glu	missense	Exon 1 of 8	NP_001238978.1	P22061
	PCMT1	NM_001252053.1		c.68C>A	p.Ala23Glu	missense	Exon 1 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.-107C>A		5_prime_UTR	Exon 1 of 8	ENSP00000420813.2	P22061-1
	PCMT1	ENST00000367384.8	TSL:1	c.-107C>A		5_prime_UTR	Exon 1 of 8	ENSP00000356354.3	P22061-2
	PCMT1	ENST00000367378.6	TSL:1	c.-107C>A		5_prime_UTR	Exon 1 of 7	ENSP00000356348.2	P22061-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1399350 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690316

African (AFR) AF: 0.00 AC: 0 AN: 31674

American (AMR) AF: 0.00 AC: 0 AN: 35714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25168

East Asian (EAS) AF: 0.00 AC: 0 AN: 35764

South Asian (SAS) AF: 0.00 AC: 0 AN: 79342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078976

Other (OTH) AF: 0.00 AC: 0 AN: 57998

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.081
PrimateAI	Pathogenic	0.82	D
Sift4G	Benign	0.38	T
Vest4		0.27
MutPred		0.29		Gain of solvent accessibility (P = 9e-04)
MVP		0.28
ClinPred		0.79	D
GERP RS		2.4
PromoterAI		0.039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.36
Mutation Taster		=95/5	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: rs564771067; hg19: chr6-150070931;