Variant 16-22534155-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000424340.7(NPIPB5):c.1172G>A(p.Arg391His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R391C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 5)

Exomes 𝑓: 0.00029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NPIPB5
ENST00000424340.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.956

Variant links:

Genes affected

NPIPB5 (HGNC:37233): (nuclear pore complex interacting protein family member B5) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NPIPB5 links:

LOC105371131 (HGNC:):

LOC105371131 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02495727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPIPB5	NM_001395849.1 linkuse as main transcript	c.1172G>A	p.Arg391His	missense_variant	7/7	ENST00000424340.7	NP_001382778.1
LOC105371131	XR_007065022.1 linkuse as main transcript	n.150+3323C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPIPB5	ENST00000424340.7 linkuse as main transcript	c.1172G>A	p.Arg391His	missense_variant	7/7	1	NM_001395849.1	ENSP00000440703	P1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

19020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000584

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000739

AC:

AN:

58152

Hom.:

AF XY:

0.000610

AC XY:

AN XY:

29494

show subpopulations

Gnomad AFR exome

AF:

0.000762

Gnomad AMR exome

AF:

0.00129

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00117

Gnomad NFE exome

AF:

0.000963

Gnomad OTH exome

AF:

0.00100

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000288

AC:

145

AN:

504278

Hom.:

Cov.:

AF XY:

0.000279

AC XY:

AN XY:

272390

show subpopulations

Gnomad4 AFR exome

AF:

0.000265

Gnomad4 AMR exome

AF:

0.000534

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000946

Gnomad4 SAS exome

AF:

0.000141

Gnomad4 FIN exome

AF:

0.0000305

Gnomad4 NFE exome

AF:

0.000349

Gnomad4 OTH exome

AF:

0.000459

GnomAD4 genome

AF:

0.000105

AC:

AN:

19042

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

9258

show subpopulations

Gnomad4 AFR

AF:

0.000387

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000520

Hom.:

ExAC

AF:

0.000743

AC:

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

Aug 02, 2021

The c.1172G>A (p.R391H) alteration is located in exon 7 (coding exon 7) of the NPIPB5 gene. This alteration results from a G to A substitution at nucleotide position 1172, causing the arginine (R) at amino acid position 391 to be replaced by a histidine (H). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

.;.;T;T;.;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.84

.;T;T;.;D;.

M_CAP

Benign

0.0027

MetaRNN

Benign

0.025

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-0.66

N;.;N;N;N;.

REVEL

Benign

0.090

Sift

Benign

0.13

T;.;T;T;T;.

Sift4G

Benign

0.13

T;T;T;T;T;T

Polyphen

1.0

.;.;D;D;.;.

Vest4

0.048, 0.064, 0.071

MVP

0.030

ClinPred

0.0078

Varity_R

0.038

gMVP

0.0063

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