Variant chr16-14951777-T-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_006985.4(NPIPA1):c.805T>C(p.Cys269Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 120,914 control chromosomes in the GnomAD database, including 4 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 4 hom., cov: 22)

Exomes 𝑓: 0.024 ( 168 hom. )

Failed GnomAD Quality Control

Consequence

NPIPA1
NM_006985.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.167

Variant links:

Genes affected

NPIPA1 (HGNC:7909): (nuclear pore complex interacting protein family member A1) Predicted to be involved in mRNA transport and protein transport. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NPIPA1 links:

PKD1P3-NPIPA1 (HGNC:):

PKD1P3-NPIPA1 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=0.061365336).

BP6

Variant 16-14951777-T-C is Benign according to our data. Variant chr16-14951777-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2646244.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPIPA1	NM_006985.4 linkuse as main transcript	c.805T>C	p.Cys269Arg	missense_variant	8/8	ENST00000328085.10
PKD1P3-NPIPA1	NR_146231.1 linkuse as main transcript	n.7082T>C		non_coding_transcript_exon_variant	39/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NPIPA1	ENST00000328085.10 linkuse as main transcript	c.805T>C	p.Cys269Arg	missense_variant	8/8	1	NM_006985.4	P1
NPIPA1	ENST00000472413.5 linkuse as main transcript	n.5062T>C		non_coding_transcript_exon_variant	28/28	2
NPIPA1	ENST00000541836.5 linkuse as main transcript	n.2650T>C		non_coding_transcript_exon_variant	20/20	5

Frequencies

GnomAD3 genomes

AF:

0.00199

AC:

240

AN:

120846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00202

Gnomad AMI

AF:

0.00257

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.000996

Gnomad EAS

AF:

0.000949

Gnomad SAS

AF:

0.00159

Gnomad FIN

AF:

0.00270

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00186

Gnomad OTH

AF:

0.00290

GnomAD3 exomes

AF:

0.00183

AC:

378

AN:

206398

Hom.:

AF XY:

0.00185

AC XY:

208

AN XY:

112588

show subpopulations

Gnomad AFR exome

AF:

0.00173

Gnomad AMR exome

AF:

0.00269

Gnomad ASJ exome

AF:

0.000735

Gnomad EAS exome

AF:

0.00283

Gnomad SAS exome

AF:

0.00333

Gnomad FIN exome

AF:

0.000731

Gnomad NFE exome

AF:

0.00130

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0237

AC:

29724

AN:

1254738

Hom.:

168

Cov.:

AF XY:

0.0241

AC XY:

15079

AN XY:

625320

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.0325

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.0496

Gnomad4 SAS exome

AF:

0.0406

Gnomad4 FIN exome

AF:

0.0359

Gnomad4 NFE exome

AF:

0.0217

Gnomad4 OTH exome

AF:

0.0229

GnomAD4 genome

AF:

0.00199

AC:

241

AN:

120914

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

115

AN XY:

58340

show subpopulations

Gnomad4 AFR

AF:

0.00204

Gnomad4 AMR

AF:

0.00246

Gnomad4 ASJ

AF:

0.000996

Gnomad4 EAS

AF:

0.000950

Gnomad4 SAS

AF:

0.00191

Gnomad4 FIN

AF:

0.00270

Gnomad4 NFE

AF:

0.00186

Gnomad4 OTH

AF:

0.00290

Alfa

AF:

0.0258

Hom.:

ExAC

AF:

0.000785

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

Jul 01, 2022

NPIPA1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.44

DEOGEN2

Benign

0.085

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.58

M_CAP

Benign

0.0081

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

PROVEAN

Pathogenic

-7.7

REVEL

Benign

0.12

Sift

Benign

0.047

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.48

MVP

0.16

MPC

4.6

ClinPred

0.076

Varity_R

0.60

gMVP

0.0073

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