Variant 1-205830326-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152491.5(PM20D1):c.1339A>T(p.Ile447Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000202 in 1,613,266 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00022 ( 2 hom. )

Consequence

PM20D1
NM_152491.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14475936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PM20D1	NM_152491.5 linkuse as main transcript	c.1339A>T	p.Ile447Phe	missense_variant	12/13	ENST00000367136.5
PM20D1	NR_135186.2 linkuse as main transcript	n.1337A>T		non_coding_transcript_exon_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PM20D1	ENST00000367136.5 linkuse as main transcript	c.1339A>T	p.Ile447Phe	missense_variant	12/13	1	NM_152491.5	P1	Q6GTS8-1
PM20D1-AS1	ENST00000656763.1 linkuse as main transcript	n.264+16741T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000227

AC:

AN:

251398

Hom.:

AF XY:

0.000287

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000216

AC:

315

AN:

1461000

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

175

AN XY:

726878

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000661

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000200

Hom.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2021

The c.1339A>T (p.I447F) alteration is located in exon 12 (coding exon 12) of the PM20D1 gene. This alteration results from a A to T substitution at nucleotide position 1339, causing the isoleucine (I) at amino acid position 447 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.36

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.050

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.014

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.27

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.019

Polyphen

0.98

Vest4

0.51

MVP

0.18

MPC

0.58

ClinPred

0.29

GERP RS

1.7

Varity_R

0.86

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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