Genetic Variant NPIPB5:p.Gly138Val (chr16-22527841-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001395849.1(NPIPB5):c.413G>T(p.Gly138Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.36 ( 4 hom., cov: 0)

Exomes 𝑓: 0.50 ( 882 hom. )

Failed GnomAD Quality Control

Consequence

NPIPB5
NM_001395849.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.160

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010704607).

BP6

Variant 16-22527841-G-T is Benign according to our data. Variant chr16-22527841-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2391055.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB5	NM_001395849.1 link	c.413G>T	p.Gly138Val	missense_variant	Exon 4 of 7	ENST00000424340.7	NP_001382778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPIPB5	ENST00000424340.7 link	c.413G>T	p.Gly138Val	missense_variant	Exon 4 of 7	1	NM_001395849.1	ENSP00000440703.1		A8MRT5

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

AN:

264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.450

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.494

AC:

2404

AN:

4864

Hom.:

AF XY:

0.497

AC XY:

1376

AN XY:

2768

show subpopulations

Gnomad AFR exome

AF:

0.556

Gnomad AMR exome

AF:

0.518

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.476

Gnomad SAS exome

AF:

0.499

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.455

Gnomad OTH exome

AF:

0.472

GnomAD4 exome

AF:

0.496

AC:

27864

AN:

56152

Hom.:

882

Cov.:

AF XY:

0.498

AC XY:

15208

AN XY:

30534

show subpopulations

Gnomad4 AFR exome

AF:

0.573

Gnomad4 AMR exome

AF:

0.537

Gnomad4 ASJ exome

AF:

0.485

Gnomad4 EAS exome

AF:

0.491

Gnomad4 SAS exome

AF:

0.519

Gnomad4 FIN exome

AF:

0.490

Gnomad4 NFE exome

AF:

0.486

Gnomad4 OTH exome

AF:

0.495

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.363

AC:

AN:

270

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

150

show subpopulations

Gnomad4 AFR

AF:

0.500

Gnomad4 AMR

AF:

0.462

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.458

Gnomad4 SAS

AF:

0.375

Gnomad4 FIN

AF:

0.500

Gnomad4 NFE

AF:

0.302

Gnomad4 OTH

AF:

0.143

Alfa

AF:

0.531

Hom.:

1508

ExAC

AF:

0.114

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

May 11, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.2

DANN

Benign

0.90

DEOGEN2

Benign

0.068

.;.;T;T;.;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00093

LIST_S2

Benign

0.65

.;T;T;.;T;.

M_CAP

Benign

0.0029

MetaRNN

Benign

0.011

T;T;T;T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Pathogenic

-5.5

D;.;D;D;D;.

REVEL

Benign

0.095

Sift

Benign

0.30

T;.;T;T;T;.

Sift4G

Benign

0.25

T;T;T;T;T;T

Polyphen

0.56

.;.;P;P;.;.

Vest4

0.10, 0.15, 0.090, 0.12

ClinPred

0.065

GERP RS

-0.91

Varity_R

0.30

gMVP

0.0022

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