Variant 1-205843751-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152491.5(PM20D1):c.743T>C(p.Met248Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00358 in 1,614,138 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 9 hom. )

Consequence

PM20D1
NM_152491.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.166

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:

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

PM20D1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0093125105).

BP6

Variant 1-205843751-A-G is Benign according to our data. Variant chr1-205843751-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 782735.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PM20D1	NM_152491.5 linkuse as main transcript	c.743T>C	p.Met248Thr	missense_variant	6/13	ENST00000367136.5
PM20D1	NR_135186.2 linkuse as main transcript	n.803T>C		non_coding_transcript_exon_variant	6/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PM20D1	ENST00000367136.5 linkuse as main transcript	c.743T>C	p.Met248Thr	missense_variant	6/13	1	NM_152491.5	P1	Q6GTS8-1
PM20D1-AS1	ENST00000656763.1 linkuse as main transcript	n.264+30166A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

383

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00390

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00271

AC:

681

AN:

251380

Hom.:

AF XY:

0.00274

AC XY:

372

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00222

Gnomad FIN exome

AF:

0.00129

Gnomad NFE exome

AF:

0.00407

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00369

AC:

5399

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

2646

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.00203

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00192

Gnomad4 FIN exome

AF:

0.00131

Gnomad4 NFE exome

AF:

0.00425

Gnomad4 OTH exome

AF:

0.00422

GnomAD4 genome

AF:

0.00251

AC:

383

AN:

152302

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

174

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00390

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00357

Hom.:

Bravo

AF:

0.00284

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00280

AC:

340

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00393

EpiControl

AF:

0.00379

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

Cadd

Benign

0.41

Dann

Benign

0.22

DEOGEN2

Benign

0.0029

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.47

M_CAP

Benign

0.0089

MetaRNN

Benign

0.0093

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.76

REVEL

Benign

0.091

Sift

Benign

0.56

Sift4G

Benign

0.55

Polyphen

0.0040

Vest4

0.30

MVP

0.014

MPC

0.11

ClinPred

0.0080

GERP RS

-8.1

Varity_R

0.071

gMVP

0.75

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