rs1323622994

Variant names:

• chr8-51831512-G-T
• rs1323622994
• NM_052937.4:c.638C>A

Variant summary

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

The NM_052937.4(PCMTD1):​c.638C>A​(p.Ala213Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,404 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PCMTD1 NM_052937.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.62
• Publications: 1 publications found

Genes affected

PCMTD1 (HGNC:30483): (protein-L-isoaspartate (D-aspartate) O-methyltransferase domain containing 1) Predicted to enable protein-L-isoaspartate (D-aspartate) O-methyltransferase activity. Predicted to be involved in protein methylation. Predicted to be located in membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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_052937.4. 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
	PCMTD1	NM_052937.4	MANE Select	c.638C>A	p.Ala213Asp	missense	Exon 5 of 6	NP_443169.2	Q96MG8-1
	PCMTD1	NM_001286782.1		c.410C>A	p.Ala137Asp	missense	Exon 3 of 4	NP_001273711.1	Q96MG8-2
	PCMTD1	NM_001363193.1		c.638C>A	p.Ala213Asp	missense	Exon 5 of 6	NP_001350122.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCMTD1	ENST00000522514.6	TSL:2 MANE Select	c.638C>A	p.Ala213Asp	missense	Exon 5 of 6	ENSP00000428099.1	Q96MG8-1
	PCMTD1	ENST00000544451.2	TSL:1	c.410C>A	p.Ala137Asp	missense	Exon 3 of 4	ENSP00000444026.1	Q96MG8-2
	PCMTD1	ENST00000360540.9	TSL:5	c.638C>A	p.Ala213Asp	missense	Exon 6 of 7	ENSP00000353739.5	Q96MG8-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461404 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727034

African (AFR) AF: 0.0000598 AC: 2 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111742

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.1	L
PhyloP100		9.6
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.44
Sift	Benign	0.21	T
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.73		Loss of sheet (P = 0.0054)
MVP		0.56
MPC		1.6
ClinPred		0.88	D
GERP RS		5.5
Varity_R		0.33
gMVP		0.97
Mutation Taster		=28/72	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

dbSNP: rs1323622994; hg19: chr8-52744072;