rs11240572

Positions:

• chr1-205838885-C-A
• chr1-205838885-C-T

Variant summary

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

The NM_152491.5(PM20D1):​c.1116+1367G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 152,276 control chromosomes in the GnomAD database, including 287 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 0.040 (287 hom., cov: 32)
• Consequence: PM20D1 NM_152491.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PM20D1	NM_152491.5	c.1116+1367G>T		intron_variant		ENST00000367136.5	NP_689704.4
PM20D1	NR_135186.2	n.1114+1367G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PM20D1	ENST00000367136.5	c.1116+1367G>T		intron_variant		1	NM_152491.5	ENSP00000356104	P1
PM20D1-AS1	ENST00000656763.1	n.264+25300C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 6016 AN: 152158 Hom.: 284 Cov.: 32

Gnomad AFR AF: 0.00753

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.0791

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0324

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0396 AC: 6032 AN: 152276 Hom.: 287 Cov.: 32 AF XY: 0.0423 AC XY: 3151 AN XY: 74474

Gnomad4 AFR AF: 0.00748

Gnomad4 AMR AF: 0.0820

Gnomad4 ASJ AF: 0.0791

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0317

Gnomad4 NFE AF: 0.0324

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0365 Hom.: 108

Bravo AF: 0.0435

Asia WGS AF: 0.140 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.19
DANN	Benign	0.80

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: rs11240572; hg19: chr1-205808013;