Genetic Variant NM_152491.5:c.1384C>T (chr1-205830281-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152491.5(PM20D1):c.1384C>T(p.Arg462Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000145 in 1,589,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

PM20D1
NM_152491.5 missense, splice_region

Scores

Splicing: ADA: 0.0001745

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2025758).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152491.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PM20D1	NM_152491.5	MANE Select	c.1384C>T	p.Arg462Cys	missense splice_region	Exon 12 of 13	NP_689704.4
	PM20D1	NR_135186.2		n.1382C>T		splice_region non_coding_transcript_exon	Exon 11 of 12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PM20D1	ENST00000367136.5	TSL:1 MANE Select	c.1384C>T	p.Arg462Cys	missense splice_region	Exon 12 of 13	ENSP00000356104.4	Q6GTS8-1
PM20D1	ENST00000460624.5	TSL:2	n.1382C>T		splice_region non_coding_transcript_exon	Exon 11 of 12
PM20D1	ENST00000461807.1	TSL:3	n.240C>T		splice_region non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251158

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000139

AC:

AN:

1437752

Hom.:

Cov.:

AF XY:

0.00000837

AC XY:

AN XY:

716602

show subpopulations

African (AFR)

AF:

0.0000910

AC:

AN:

32954

American (AMR)

AF:

0.00

AC:

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26004

East Asian (EAS)

AF:

0.00

AC:

AN:

39594

South Asian (SAS)

AF:

0.00

AC:

AN:

85692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.0000138

AC:

AN:

1090076

Other (OTH)

AF:

0.0000335

AC:

AN:

59658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.410

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41414

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68024

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.036

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.85

M_CAP

Benign

0.0090

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

0.0

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.085

Sift

Benign

0.039

Sift4G

Benign

0.088

Polyphen

0.86

Vest4

0.28

MutPred

0.63

Loss of catalytic residue at R462 (P = 0.0276)

MVP

0.076

MPC

0.28

ClinPred

0.67

GERP RS

0.20

Varity_R

0.18

gMVP

0.75

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00017

dbscSNV1_RF

Benign

0.016

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over