Genetic Variant PM20D1:c.257-50T>C (chr1-205845607-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152491.5(PM20D1):c.257-50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 1,491,854 control chromosomes in the GnomAD database, including 1,956 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.053 ( 285 hom., cov: 32)

Exomes 𝑓: 0.047 ( 1671 hom. )

Consequence

PM20D1
NM_152491.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.665

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PM20D1	NM_152491.5 link	c.257-50T>C		intron_variant	Intron 2 of 12	ENST00000367136.5	NP_689704.4	Q6GTS8-1
PM20D1	NR_135186.2 link	n.317-50T>C		intron_variant	Intron 2 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PM20D1	ENST00000367136.5 link	c.257-50T>C		intron_variant	Intron 2 of 12	1	NM_152491.5	ENSP00000356104.4		Q6GTS8-1

Frequencies

GnomAD3 genomes

AF:

0.0534

AC:

8127

AN:

152162

Hom.:

286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0860

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0332

Gnomad ASJ

AF:

0.0585

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0493

Gnomad FIN

AF:

0.0314

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0465

Gnomad OTH

AF:

0.0478

GnomAD2 exomes

AF:

0.0413

AC:

9601

AN:

232434

AF XY:

0.0427

show subpopulations

Gnomad AFR exome

AF:

0.0896

Gnomad AMR exome

AF:

0.0170

Gnomad ASJ exome

AF:

0.0555

Gnomad EAS exome

AF:

0.0000565

Gnomad FIN exome

AF:

0.0324

Gnomad NFE exome

AF:

0.0456

Gnomad OTH exome

AF:

0.0387

GnomAD4 exome

AF:

0.0472

AC:

63162

AN:

1339572

Hom.:

1671

Cov.:

AF XY:

0.0476

AC XY:

31803

AN XY:

668554

show subpopulations

African (AFR)

AF:

0.0932

AC:

2846

AN:

30538

American (AMR)

AF:

0.0196

AC:

819

AN:

41846

Ashkenazi Jewish (ASJ)

AF:

0.0538

AC:

1322

AN:

24566

East Asian (EAS)

AF:

0.000129

AC:

AN:

38832

South Asian (SAS)

AF:

0.0548

AC:

4461

AN:

81418

European-Finnish (FIN)

AF:

0.0365

AC:

1809

AN:

49606

Middle Eastern (MID)

AF:

0.0759

AC:

414

AN:

5456

European-Non Finnish (NFE)

AF:

0.0483

AC:

48831

AN:

1011168

Other (OTH)

AF:

0.0473

AC:

2655

AN:

56142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2956

5912

8869

11825

14781

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1860

3720

5580

7440

9300

<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:

0.0534

AC:

8137

AN:

152282

Hom.:

285

Cov.:

AF XY:

0.0521

AC XY:

3876

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0861

AC:

3575

AN:

41532

American (AMR)

AF:

0.0332

AC:

508

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0585

AC:

203

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0491

AC:

237

AN:

4822

European-Finnish (FIN)

AF:

0.0314

AC:

333

AN:

10616

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0465

AC:

3160

AN:

68024

Other (OTH)

AF:

0.0473

AC:

100

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

399

798

1196

1595

1994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0475

Hom.:

277

Bravo

AF:

0.0543

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.6

(source)

DANN

Benign

0.83

PhyloP100

-0.67

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over