Variant chr16-15363750-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001277325.2(NPIPA5):c.962C>T(p.Pro321Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000515 in 1,416,716 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000095 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000047 ( 3 hom. )

Consequence

NPIPA5
NM_001277325.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 0.00

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13800871).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPIPA5	NM_001277325.2 linkuse as main transcript	c.962C>T	p.Pro321Leu	missense_variant	8/8	ENST00000360151.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPIPA5	ENST00000360151.9 linkuse as main transcript	c.962C>T	p.Pro321Leu	missense_variant	8/8	1	NM_001277325.2		E9PKD4-1

Frequencies

GnomAD3 genomes

AF:

0.0000953

AC:

AN:

125868

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:

0.000272

Gnomad FIN

AF:

0.000264

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000151

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000481

AC:

AN:

207992

Hom.:

AF XY:

0.0000611

AC XY:

AN XY:

114592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000359

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000180

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000396

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000473

AC:

AN:

1290758

Hom.:

Cov.:

AF XY:

0.0000515

AC XY:

AN XY:

641274

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000899

Gnomad4 SAS exome

AF:

0.0000768

Gnomad4 FIN exome

AF:

0.0000305

Gnomad4 NFE exome

AF:

0.0000217

Gnomad4 OTH exome

AF:

0.0000195

GnomAD4 genome

AF:

0.0000953

AC:

AN:

125958

Hom.:

Cov.:

AF XY:

0.0000990

AC XY:

AN XY:

60608

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000273

Gnomad4 FIN

AF:

0.000264

Gnomad4 NFE

AF:

0.000151

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000849

Hom.:

ExAC

AF:

0.00000869

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Oromandibular-limb hypogenesis spectrum

Uncertain:1

Uncertain significance, no assertion criteria provided

research

CHU Sainte-Justine Research Center, University of Montreal

Aug 12, 2016

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.023

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.50

M_CAP

Benign

0.018

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PROVEAN

Benign

-2.1

REVEL

Benign

0.089

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0060

Vest4

0.097

MutPred

0.50

Loss of glycosylation at P321 (P = 0.0143);

MVP

0.043

MPC

2.0

ClinPred

0.14

Varity_R

0.076

gMVP

0.010

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