rs16916856

Variant names:

• chr8-51826590-T-C
• rs16916856
• NM_052937.4:c.706+4854A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000522514.6(PCMTD1):​c.706+4854A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,242 control chromosomes in the GnomAD database, including 1,239 homozygotes. 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: 𝑓 0.11 (1239 hom., cov: 32)
• Consequence: PCMTD1 ENST00000522514.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000522514.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCMTD1	NM_052937.4	MANE Select	c.706+4854A>G		intron	N/A	NP_443169.2
	PCMTD1	NM_001286782.1		c.478+4854A>G		intron	N/A	NP_001273711.1
	PCMTD1	NM_001286783.2		c.178+4854A>G		intron	N/A	NP_001273712.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCMTD1	ENST00000522514.6	TSL:2 MANE Select	c.706+4854A>G		intron	N/A	ENSP00000428099.1
	PCMTD1	ENST00000544451.2	TSL:1	c.478+4854A>G		intron	N/A	ENSP00000444026.1
	PCMTD1	ENST00000360540.9	TSL:5	c.706+4854A>G		intron	N/A	ENSP00000353739.5

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16538 AN: 152124 Hom.: 1234 Cov.: 32

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0836

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.117

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.109 AC: 16554 AN: 152242 Hom.: 1239 Cov.: 32 AF XY: 0.116 AC XY: 8623 AN XY: 74434

African (AFR) AF: 0.0242 AC: 1004 AN: 41554

American (AMR) AF: 0.0834 AC: 1276 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3472

East Asian (EAS) AF: 0.166 AC: 861 AN: 5186

South Asian (SAS) AF: 0.131 AC: 633 AN: 4826

European-Finnish (FIN) AF: 0.238 AC: 2518 AN: 10584

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9414 AN: 68008

Other (OTH) AF: 0.118 AC: 250 AN: 2114

Alfa AF: 0.125 Hom.: 971

Bravo AF: 0.0919

Asia WGS AF: 0.176 AC: 613 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.58
DANN	Benign	0.88
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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: rs16916856; hg19: chr8-52739150;