Variant 1-205832744-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152491.5(PM20D1):c.1139T>C(p.Ile380Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 1,604,978 control chromosomes in the GnomAD database, including 199,557 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 (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.45 ( 16412 hom., cov: 32)

Exomes 𝑓: 0.49 ( 183145 hom. )

Consequence

PM20D1
NM_152491.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.693

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.4879317E-4).

BP6

Variant 1-205832744-A-G is Benign according to our data. Variant chr1-205832744-A-G is described in ClinVar as [Benign]. Clinvar id is 1297905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PM20D1	NM_152491.5 link	c.1139T>C	p.Ile380Thr	missense_variant	11/13	ENST00000367136.5	NP_689704.4	Q6GTS8-1
PM20D1	NR_135186.2 link	n.1137T>C		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.1139T>C	p.Ile380Thr	missense_variant	11/13	1	NM_152491.5	ENSP00000356104.4		Q6GTS8-1

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68250

AN:

151924

Hom.:

16405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.405

Gnomad AMI

AF:

0.412

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.474

Gnomad EAS

AF:

0.00712

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.563

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.525

Gnomad OTH

AF:

0.465

GnomAD3 exomes

AF:

0.407

AC:

99191

AN:

243878

Hom.:

24007

AF XY:

0.409

AC XY:

53899

AN XY:

131766

show subpopulations

Gnomad AFR exome

AF:

0.399

Gnomad AMR exome

AF:

0.249

Gnomad ASJ exome

AF:

0.474

Gnomad EAS exome

AF:

0.00283

Gnomad SAS exome

AF:

0.235

Gnomad FIN exome

AF:

0.560

Gnomad NFE exome

AF:

0.529

Gnomad OTH exome

AF:

0.445

GnomAD4 exome

AF:

0.487

AC:

707362

AN:

1452936

Hom.:

183145

Cov.:

AF XY:

0.480

AC XY:

346716

AN XY:

722006

show subpopulations

Gnomad4 AFR exome

AF:

0.401

Gnomad4 AMR exome

AF:

0.259

Gnomad4 ASJ exome

AF:

0.474

Gnomad4 EAS exome

AF:

0.00193

Gnomad4 SAS exome

AF:

0.240

Gnomad4 FIN exome

AF:

0.560

Gnomad4 NFE exome

AF:

0.533

Gnomad4 OTH exome

AF:

0.457

GnomAD4 genome

AF:

0.449

AC:

68274

AN:

152042

Hom.:

16412

Cov.:

AF XY:

0.441

AC XY:

32811

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.405

Gnomad4 AMR

AF:

0.371

Gnomad4 ASJ

AF:

0.474

Gnomad4 EAS

AF:

0.00733

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.563

Gnomad4 NFE

AF:

0.525

Gnomad4 OTH

AF:

0.459

Alfa

AF:

0.493

Hom.:

48504

Bravo

AF:

0.431

TwinsUK

AF:

0.549

AC:

2037

ALSPAC

AF:

0.546

AC:

2104

ESP6500AA

AF:

0.402

AC:

1770

ESP6500EA

AF:

0.523

AC:

4497

ExAC

AF:

0.408

AC:

49506

Asia WGS

AF:

0.128

AC:

448

AN:

3478

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	clinical testing	GeneDx	Jan 11, 2019	This variant is associated with the following publications: (PMID: 29874175) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.41

DANN

Benign

0.50

DEOGEN2

Benign

0.0031

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.66

MetaRNN

Benign

0.00045

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.93

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.30

REVEL

Benign

0.046

Sift

Benign

0.60

Sift4G

Benign

0.66

Polyphen

0.016

Vest4

0.054

MPC

0.13

ClinPred

0.0039

GERP RS

-0.11

Varity_R

0.083

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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