Genetic Variant NPEPL1:c.-41-261G>A (chr20-58691463-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_001204872.2(NPEPL1):c.-41-261G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00522 in 648,678 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 7 hom., cov: 23)

Exomes 𝑓: 0.0051 ( 14 hom. )

Consequence

NPEPL1
NM_001204872.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.532

Variant links:

Genes affected

NPEPL1 (HGNC:16244): (aminopeptidase like 1) Predicted to enable manganese ion binding activity and metalloaminopeptidase activity. Predicted to be involved in proteolysis. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NPEPL1 links:

STX16-NPEPL1 (HGNC:41993): (STX16-NPEPL1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring syntaxin 16 (STX16) and aminopeptidase-like 1 (NPEPL1) genes on chromosome 20. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

STX16-NPEPL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 20-58691463-G-A is Benign according to our data. Variant chr20-58691463-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652433.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
NPEPL1	NM_001204872.2 link	c.-41-261G>A	intron_variant	Intron 1 of 12	NP_001191801.1	Q8NDH3-4
NPEPL1	NM_001204873.2 link	c.-51-261G>A	intron_variant	Intron 1 of 12	NP_001191802.1	Q8NDH3-5
STX16-NPEPL1	NR_037945.1 link	n.1880G>A	non_coding_transcript_exon_variant	Exon 10 of 23

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
NPEPL1	ENST00000525967.5 link	c.-41-261G>A	intron_variant	Intron 1 of 12	1	ENSP00000434810.1	Q8NDH3-4
STX16-NPEPL1	ENST00000530122.1 link	n.1126G>A	non_coding_transcript_exon_variant	Exon 10 of 23	5	ENSP00000457522.1	H3BU86
NPEPL1	ENST00000525817.5 link	c.-51-261G>A	intron_variant	Intron 1 of 12	2	ENSP00000437112.1	Q8NDH3-5
STX16-NPEPL1	ENST00000413559.1 link	n.75-261G>A	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.00569

AC:

746

AN:

131120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00163

Gnomad AMI

AF:

0.0348

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.00349

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000485

Gnomad FIN

AF:

0.00251

Gnomad MID

AF:

0.00467

Gnomad NFE

AF:

0.00723

Gnomad OTH

AF:

0.0126

GnomAD3 exomes

AF:

0.00443

AC:

572

AN:

129210

Hom.:

AF XY:

0.00436

AC XY:

307

AN XY:

70422

show subpopulations

Gnomad AFR exome

AF:

0.00126

Gnomad AMR exome

AF:

0.00623

Gnomad ASJ exome

AF:

0.00233

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000524

Gnomad FIN exome

AF:

0.000379

Gnomad NFE exome

AF:

0.00692

Gnomad OTH exome

AF:

0.00752

GnomAD4 exome

AF:

0.00510

AC:

2639

AN:

517482

Hom.:

Cov.:

AF XY:

0.00499

AC XY:

1404

AN XY:

281136

show subpopulations

Gnomad4 AFR exome

AF:

0.00132

Gnomad4 AMR exome

AF:

0.00768

Gnomad4 ASJ exome

AF:

0.00299

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000753

Gnomad4 FIN exome

AF:

0.00160

Gnomad4 NFE exome

AF:

0.00682

Gnomad4 OTH exome

AF:

0.00634

GnomAD4 genome

AF:

0.00569

AC:

746

AN:

131196

Hom.:

Cov.:

AF XY:

0.00533

AC XY:

327

AN XY:

61330

show subpopulations

Gnomad4 AFR

AF:

0.00163

Gnomad4 AMR

AF:

0.0132

Gnomad4 ASJ

AF:

0.00349

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000486

Gnomad4 FIN

AF:

0.00251

Gnomad4 NFE

AF:

0.00723

Gnomad4 OTH

AF:

0.0126

Alfa

AF:

0.00552

Hom.:

Bravo

AF:

0.00578

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NPEPL1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

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