Variant 15-24676165-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018958.3(NPAP1):c.298C>T(p.Leu100Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,577,772 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 85 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 92 hom. )

Consequence

NPAP1
NM_018958.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.869

Variant links:

Genes affected

NPAP1 (HGNC:1190): (nuclear pore associated protein 1) This intronless retrogene is located in the Prader-Willi syndrome region on chromosome 15. This gene exhibits tissue-specific imprinting. Expression in adult testis and brain is biallelic, while expression in fetal brain is monoallelic and only from the paternal chromosome. The encoded protein is associated with the nuclear pore complex. [provided by RefSeq, Mar 2021]

NPAP1 links:

ENSG00000286110 (HGNC:):

ENSG00000286110 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 15-24676165-C-T is Benign according to our data. Variant chr15-24676165-C-T is described in ClinVar as [Benign]. Clinvar id is 783700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.869 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAP1	NM_018958.3 linkuse as main transcript	c.298C>T	p.Leu100Leu	synonymous_variant	1/1	ENST00000329468.5	NP_061831.2	Q9NZP6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAP1	ENST00000329468.5 linkuse as main transcript	c.298C>T	p.Leu100Leu	synonymous_variant	1/1	6	NM_018958.3	ENSP00000333735.3		Q9NZP6

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2911

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0671

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00595

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:

0.000221

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00527

AC:

1127

AN:

214042

Hom.:

AF XY:

0.00399

AC XY:

462

AN XY:

115840

show subpopulations

Gnomad AFR exome

AF:

0.0691

Gnomad AMR exome

AF:

0.00297

Gnomad ASJ exome

AF:

0.000144

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000413

Gnomad FIN exome

AF:

0.0000512

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.00298

GnomAD4 exome

AF:

0.00188

AC:

2681

AN:

1425520

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

1176

AN XY:

706744

show subpopulations

Gnomad4 AFR exome

AF:

0.0681

Gnomad4 AMR exome

AF:

0.00344

Gnomad4 ASJ exome

AF:

0.0000853

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000112

Gnomad4 FIN exome

AF:

0.0000391

Gnomad4 NFE exome

AF:

0.0000958

Gnomad4 OTH exome

AF:

0.00402

GnomAD4 genome

AF:

0.0192

AC:

2924

AN:

152252

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

1358

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0672

Gnomad4 AMR

AF:

0.00595

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0141

Hom.:

Bravo

AF:

0.0219

Asia WGS

AF:

0.00318

AC:

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	Labcorp Genetics (formerly Invitae), Labcorp	Apr 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.9

DANN

Benign

0.63

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