Variant chr16-15370063-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001277325.2(NPIPA5):c.249T>G(p.Asp83Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00554 in 1,507,420 control chromosomes in the GnomAD database, including 389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 21 hom., cov: 19)

Exomes 𝑓: 0.0057 ( 368 hom. )

Consequence

NPIPA5
NM_001277325.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.777

Variant links:

Genes affected

NPIPA5 (HGNC:41980): (nuclear pore complex interacting protein family member A5) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NPIPA5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009825617).

BP6

Variant 16-15370063-A-C is Benign according to our data. Variant chr16-15370063-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3388337.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPIPA5	NM_001277325.2 link	c.249T>G	p.Asp83Glu	missense_variant	3/8	ENST00000360151.9	NP_001264254.1	E9PKD4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NPIPA5	ENST00000360151.9 link	c.249T>G	p.Asp83Glu	missense_variant	3/8	1	NM_001277325.2	ENSP00000433597.1	E9PKD4-1
NPIPA5	ENST00000543801.5 link	c.249T>G	p.Asp83Glu	missense_variant	3/8	1		ENSP00000441072.1	E9PKD4-2
NPIPA5	ENST00000534094.1 link	c.306T>G	p.Asp102Glu	missense_variant	3/7	5		ENSP00000435611.1	E9PJ88

Frequencies

GnomAD3 genomes

AF:

0.00429

AC:

552

AN:

128790

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000997

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00554

Gnomad ASJ

AF:

0.00649

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000852

Gnomad FIN

AF:

0.000798

Gnomad MID

AF:

0.00658

Gnomad NFE

AF:

0.00684

Gnomad OTH

AF:

0.00296

GnomAD3 exomes

AF:

0.00424

AC:

247

AN:

58304

Hom.:

AF XY:

0.00443

AC XY:

129

AN XY:

29094

show subpopulations

Gnomad AFR exome

AF:

0.00144

Gnomad AMR exome

AF:

0.00478

Gnomad ASJ exome

AF:

0.00753

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00177

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00653

Gnomad OTH exome

AF:

0.00404

GnomAD4 exome

AF:

0.00565

AC:

7795

AN:

1378546

Hom.:

368

Cov.:

AF XY:

0.00564

AC XY:

3884

AN XY:

688496

show subpopulations

Gnomad4 AFR exome

AF:

0.000888

Gnomad4 AMR exome

AF:

0.00367

Gnomad4 ASJ exome

AF:

0.00635

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00242

Gnomad4 FIN exome

AF:

0.000505

Gnomad4 NFE exome

AF:

0.00653

Gnomad4 OTH exome

AF:

0.00466

GnomAD4 genome

AF:

0.00428

AC:

551

AN:

128874

Hom.:

Cov.:

AF XY:

0.00409

AC XY:

251

AN XY:

61296

show subpopulations

Gnomad4 AFR

AF:

0.000994

Gnomad4 AMR

AF:

0.00554

Gnomad4 ASJ

AF:

0.00649

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000853

Gnomad4 FIN

AF:

0.000798

Gnomad4 NFE

AF:

0.00682

Gnomad4 OTH

AF:

0.00293

Alfa

AF:

0.00409

Hom.:

ExAC

AF:

0.00268

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

NPIPA5: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.096

T;.;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.85

T;.;T

MetaRNN

Benign

0.0098

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.3

M;M;.

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.14

MutPred

0.65

Gain of helix (P = 0.062);Gain of helix (P = 0.062);.;

MVP

0.28

MPC

1.7

ClinPred

0.052

Varity_R

0.48

gMVP

0.0013

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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