Variant 1-205832628-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_152491.5(PM20D1):c.1255G>A(p.Val419Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00975 in 1,614,070 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0099 ( 84 hom. )

Consequence

PM20D1
NM_152491.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.10

Variant links:

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 links:

ENSG00000286619 (HGNC:27633): (PM20D1 antisense RNA 1)

ENSG00000286619 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004850149).

BP6

Variant 1-205832628-C-T is Benign according to our data. Variant chr1-205832628-C-T is described in ClinVar as [Benign]. Clinvar id is 717694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PM20D1	NM_152491.5 link	c.1255G>A	p.Val419Ile	missense_variant	11/13	ENST00000367136.5	NP_689704.4	Q6GTS8-1
PM20D1	NR_135186.2 link	n.1253G>A		non_coding_transcript_exon_variant	10/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PM20D1	ENST00000367136.5 link	c.1255G>A	p.Val419Ile	missense_variant	11/13	1	NM_152491.5	ENSP00000356104.4		Q6GTS8-1

Frequencies

GnomAD3 genomes

AF:

0.00791

AC:

1204

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00343

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.00256

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0109

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00775

AC:

1948

AN:

251334

Hom.:

AF XY:

0.00757

AC XY:

1028

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.00295

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.0123

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.00848

GnomAD4 exome

AF:

0.00994

AC:

14534

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00983

AC XY:

7152

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00284

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.0104

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.0116

Gnomad4 OTH exome

AF:

0.00732

GnomAD4 genome

AF:

0.00790

AC:

1203

AN:

152252

Hom.:

Cov.:

AF XY:

0.00752

AC XY:

560

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00342

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0109

Gnomad4 NFE

AF:

0.0121

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00994

Hom.:

Bravo

AF:

0.00691

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.0119

AC:

102

ExAC

AF:

0.00787

AC:

955

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00981

EpiControl

AF:

0.00777

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0035

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.27

REVEL

Benign

0.026

Sift

Benign

0.43

Sift4G

Benign

0.33

Polyphen

0.046

Vest4

0.060

MVP

0.040

MPC

0.086

ClinPred

0.0091

GERP RS

1.3

Varity_R

0.057

gMVP

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over