8-51831473-T-C

Variant names:

• chr8-51831473-T-C
• rs1404898056
• NM_052937.4:c.677A>G

Variant summary

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

The NM_052937.4(PCMTD1):​c.677A>G​(p.Asp226Gly) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D226V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PCMTD1 NM_052937.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.18
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20212647).

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.677A>G	p.Asp226Gly	missense	Exon 5 of 6	NP_443169.2	Q96MG8-1
	PCMTD1	NM_001286782.1		c.449A>G	p.Asp150Gly	missense	Exon 3 of 4	NP_001273711.1	Q96MG8-2
	PCMTD1	NM_001363193.1		c.677A>G	p.Asp226Gly	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.677A>G	p.Asp226Gly	missense	Exon 5 of 6	ENSP00000428099.1	Q96MG8-1
	PCMTD1	ENST00000544451.2	TSL:1	c.449A>G	p.Asp150Gly	missense	Exon 3 of 4	ENSP00000444026.1	Q96MG8-2
	PCMTD1	ENST00000360540.9	TSL:5	c.677A>G	p.Asp226Gly	missense	Exon 6 of 7	ENSP00000353739.5	Q96MG8-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.094	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	2.0	M
PhyloP100		7.2
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.45
MutPred		0.39		Gain of sheet (P = 0.0101)
MVP		0.53
MPC		1.4
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.43
gMVP		0.88
Mutation Taster		=24/76	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1404898056; hg19: chr8-52744033;