Genetic Variant NPIPB5:p.Ala297Val (chr16-22533873-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001395849.1(NPIPB5):c.890C>T(p.Ala297Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 3)

Exomes 𝑓: 0.000078 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NPIPB5
NM_001395849.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.68

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07865304).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395849.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPIPB5	NM_001395849.1	MANE Select	c.890C>T	p.Ala297Val	missense	Exon 7 of 7	NP_001382778.1	A8MRT5
NPIPB5	NM_001135865.3		c.890C>T	p.Ala297Val	missense	Exon 9 of 9	NP_001129337.1	A8MRT5
NPIPB5	NM_001395850.1		c.890C>T	p.Ala297Val	missense	Exon 8 of 8	NP_001382779.1	A8MRT5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPIPB5	ENST00000424340.7	TSL:1 MANE Select	c.890C>T	p.Ala297Val	missense	Exon 7 of 7	ENSP00000440703.1	A8MRT5
NPIPB5	ENST00000528249.5	TSL:1	c.890C>T	p.Ala297Val	missense	Exon 7 of 7	ENSP00000431553.1	E9PKP1
NPIPB5	ENST00000517539.6	TSL:5	c.890C>T	p.Ala297Val	missense	Exon 8 of 8	ENSP00000430633.1	A8MRT5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

4244

Hom.:

Cov.:

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000780

AC:

AN:

435860

Hom.:

Cov.:

AF XY:

0.0000728

AC XY:

AN XY:

233450

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000161

AC:

AN:

12426

American (AMR)

AF:

0.0000527

AC:

AN:

18970

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13080

East Asian (EAS)

AF:

0.000134

AC:

AN:

29920

South Asian (SAS)

AF:

0.0000662

AC:

AN:

45332

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1898

European-Non Finnish (NFE)

AF:

0.0000885

AC:

AN:

259816

Other (OTH)

AF:

0.0000401

AC:

AN:

24912

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.337

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

4244

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

2316

African (AFR)

AF:

0.00

AC:

AN:

1376

American (AMR)

AF:

0.00

AC:

AN:

508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

100

East Asian (EAS)

AF:

0.00

AC:

AN:

106

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1788

Other (OTH)

AF:

0.00

AC:

AN:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.0

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0081

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.52

M_CAP

Benign

0.0018

MetaRNN

Benign

0.079

MetaSVM

Benign

-1.1

PhyloP100

-1.7

PROVEAN

Benign

-0.33

REVEL

Benign

0.15

Sift

Benign

0.44

Sift4G

Benign

0.50

Polyphen

0.60

Vest4

0.031

MutPred

0.53

Gain of relative solvent accessibility (P = 0.0023)

MVP

0.014

ClinPred

0.29

Varity_R

0.061

gMVP

0.011

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over