8-51820467-G-C

Variant names:

• chr8-51820467-G-C
• rs769943059
• NM_052937.4:c.958C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052937.4(PCMTD1):​c.958C>G​(p.His320Asp) 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. 15/21 in silico tools predict 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. H320N) 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: 1.40

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049494088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCMTD1	NM_052937.4	c.958C>G	p.His320Asp	missense_variant	Exon 6 of 6	ENST00000522514.6	NP_443169.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCMTD1	ENST00000522514.6	c.958C>G	p.His320Asp	missense_variant	Exon 6 of 6	2	NM_052937.4	ENSP00000428099.1
PCMTD1	ENST00000544451.2	c.730C>G	p.His244Asp	missense_variant	Exon 4 of 4	1		ENSP00000444026.1
PCMTD1	ENST00000360540.9	c.958C>G	p.His320Asp	missense_variant	Exon 7 of 7	5		ENSP00000353739.5
PCMTD1	ENST00000519559.1	n.884C>G		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.5
DANN	Benign	0.61
DEOGEN2	Benign	0.022	T;T;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.11	T;.;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.049	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	.;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.82	N;N;N
REVEL	Benign	0.037
Sift	Benign	0.47	T;T;T
Sift4G	Benign	0.63	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.081
MutPred		0.14		.;Gain of relative solvent accessibility (P = 0.0507);Gain of relative solvent accessibility (P = 0.0507);
MVP		0.27
MPC		.;2.61916662686E-4;.
ClinPred		0.020	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.037
gMVP		0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs769943059; hg19: chr8-52733027;