rs17348507

Positions:

• chr1-205845607-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152491.5(PM20D1):​c.257-50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 1,491,854 control chromosomes in the GnomAD database, including 1,956 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 0.053 (285 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1671 hom.)
• Consequence: PM20D1 NM_152491.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665

Genes affected

PM20D1 (HGNC:26518): (peptidase M20 domain containing 1) Enables hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides. Involved in several processes, including amide biosynthetic process; cellular amide catabolic process; and negative regulation of neuron death. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

PM20D1-AS1 (HGNC:27633): (PM20D1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PM20D1	NM_152491.5	c.257-50T>C		intron_variant		ENST00000367136.5
PM20D1	NR_135186.2	n.317-50T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PM20D1	ENST00000367136.5	c.257-50T>C		intron_variant		1	NM_152491.5	P1
PM20D1-AS1	ENST00000656763.1	n.264+32022A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8127 AN: 152162 Hom.: 286 Cov.: 32

Gnomad AFR AF: 0.0860

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0465

Gnomad OTH AF: 0.0478

GnomAD3 exomes AF: 0.0413 AC: 9601 AN: 232434 Hom.: 263 AF XY: 0.0427 AC XY: 5379 AN XY: 125884

Gnomad AFR exome AF: 0.0896

Gnomad AMR exome AF: 0.0170

Gnomad ASJ exome AF: 0.0555

Gnomad EAS exome AF: 0.0000565

Gnomad SAS exome AF: 0.0539

Gnomad FIN exome AF: 0.0324

Gnomad NFE exome AF: 0.0456

Gnomad OTH exome AF: 0.0387

GnomAD4 exome AF: 0.0472 AC: 63162 AN: 1339572 Hom.: 1671 Cov.: 21 AF XY: 0.0476 AC XY: 31803 AN XY: 668554

Gnomad4 AFR exome AF: 0.0932

Gnomad4 AMR exome AF: 0.0196

Gnomad4 ASJ exome AF: 0.0538

Gnomad4 EAS exome AF: 0.000129

Gnomad4 SAS exome AF: 0.0548

Gnomad4 FIN exome AF: 0.0365

Gnomad4 NFE exome AF: 0.0483

Gnomad4 OTH exome AF: 0.0473

GnomAD4 genome AF: 0.0534 AC: 8137 AN: 152282 Hom.: 285 Cov.: 32 AF XY: 0.0521 AC XY: 3876 AN XY: 74456

Gnomad4 AFR AF: 0.0861

Gnomad4 AMR AF: 0.0332

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0491

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0465

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0468 Hom.: 209

Bravo AF: 0.0543

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.6
DANN	Benign	0.83

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: rs17348507; hg19: chr1-205814735;