Variant chr16-14945938-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006985.4(NPIPA1):c.394C>T(p.Arg132Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 8)

Exomes 𝑓: 0.00020 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NPIPA1
NM_006985.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.734

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11242929).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPIPA1	NM_006985.4 linkuse as main transcript	c.394C>T	p.Arg132Cys	missense_variant	4/8	ENST00000328085.10
PKD1P3-NPIPA1	NR_146231.1 linkuse as main transcript	n.6601C>T		non_coding_transcript_exon_variant	34/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPIPA1	ENST00000328085.10 linkuse as main transcript	c.394C>T	p.Arg132Cys	missense_variant	4/8	1	NM_006985.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

67838

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00147

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000630

Gnomad SAS

AF:

0.000656

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000108

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000202

AC:

AN:

441574

Hom.:

Cov.:

AF XY:

0.000195

AC XY:

AN XY:

231344

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.000757

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000198

Gnomad4 SAS exome

AF:

0.000158

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000117

Gnomad4 OTH exome

AF:

0.000389

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000250

AC:

AN:

67880

Hom.:

Cov.:

AF XY:

0.000300

AC XY:

AN XY:

30040

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.00147

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000631

Gnomad4 SAS

AF:

0.000654

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000108

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 31, 2023

The c.394C>T (p.R132C) alteration is located in exon 4 (coding exon 4) of the NPIPA1 gene. This alteration results from a C to T substitution at nucleotide position 394, causing the arginine (R) at amino acid position 132 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.058

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0010

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.55

N;.

MutationTaster

Benign

1.0

PROVEAN

Uncertain

-2.5

N;D

REVEL

Benign

0.17

Sift

Benign

0.040

D;D

Sift4G

Uncertain

0.041

D;D

Polyphen

1.0

D;.

Vest4

0.053

MutPred

0.54

Loss of disorder (P = 0.0433);.;

MVP

0.030

MPC

2.1

ClinPred

0.034

GERP RS

-0.22

Varity_R

0.10

gMVP

0.0013

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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