Genetic Variant NPIPB3:p.Glu90Gln (chr16-21405020-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_130464.3(NPIPB3):c.916G>C(p.Glu306Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 5)

Exomes 𝑓: 0.00030 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

NPIPB3
NM_130464.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.32

Variant links:

Genes affected

NPIPB3 (HGNC:28989): (nuclear pore complex interacting protein family member B3) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NPIPB3 links:

ENSG00000290192 (HGNC:):

ENSG00000290192 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=0.010545284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB3	NM_130464.3 link	c.916G>C	p.Glu306Gln	missense_variant	Exon 8 of 12		NP_569731.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
NPIPB3	ENST00000542817.1 link	c.268G>C	p.Glu90Gln	missense_variant	Exon 1 of 2	5	ENSP00000444096.1	Q92617-4
NPIPB3	ENST00000504841.6 link	c.916G>C	p.Glu306Gln	missense_variant	Exon 7 of 7	1	ENSP00000446048.1	F5H4N5
ENSG00000290192	ENST00000703536.1 link	n.239+3826C>G		intron_variant	Intron 2 of 2
NPIPB3	ENST00000419180.6 link	c.*153G>C		downstream_gene_variant		3	ENSP00000413141.2	C9K082

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

25584

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00345

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:

0.00151

AC:

AN:

54808

Hom.:

AF XY:

0.000951

AC XY:

AN XY:

27342

show subpopulations

Gnomad AFR exome

AF:

0.00932

Gnomad AMR exome

AF:

0.000563

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00399

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000947

Gnomad OTH exome

AF:

0.00104

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000298

AC:

203

AN:

681982

Hom.:

Cov.:

AF XY:

0.000244

AC XY:

AN XY:

364052

show subpopulations

Gnomad4 AFR exome

AF:

0.00627

Gnomad4 AMR exome

AF:

0.000302

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000299

Gnomad4 SAS exome

AF:

0.000595

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000322

Gnomad4 OTH exome

AF:

0.000725

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000625

AC:

AN:

25594

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

13288

show subpopulations

Gnomad4 AFR

AF:

0.00344

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:

0.000149

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.916G>C (p.E306Q) alteration is located in exon 8 (coding exon 7) of the NPIPB3 gene. This alteration results from a G to C substitution at nucleotide position 916, causing the glutamic acid (E) at amino acid position 306 to be replaced by a glutamine (Q). 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

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.3

DANN

Uncertain

0.99

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.049

Sift

Uncertain

0.0090

D;D

Sift4G

Benign

0.28

T;D

Vest4

0.13

MVP

0.043

ClinPred

0.035

gMVP

0.015

Splicing

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