Genetic Variant NPIPB7:p.Ser255Cys (chr16-28456905-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001396030.1(NPIPB7):c.764C>G(p.Ser255Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00037 ( 1 hom., cov: 17)

Exomes 𝑓: 0.00045 ( 60 hom. )

Failed GnomAD Quality Control

Consequence

NPIPB7
NM_001396030.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0640

Variant links:

Genes affected

NPIPB7 (HGNC:33832): (nuclear pore complex interacting protein family member B7) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NPIPB7 links:

ENSG00000261832 (HGNC:):

ENSG00000261832 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.066521555).

BP6

Variant 16-28456905-G-C is Benign according to our data. Variant chr16-28456905-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2646346.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB7	NM_001396030.1 link	c.764C>G	p.Ser255Cys	missense_variant	Exon 7 of 7	ENST00000452313.6	NP_001382959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPIPB7	ENST00000452313.6 link	c.764C>G	p.Ser255Cys	missense_variant	Exon 7 of 7	5	NM_001396030.1	ENSP00000405348.1		O75200
ENSG00000261832	ENST00000637378.1 link	c.926C>G	p.Ser309Cys	missense_variant	Exon 10 of 10	5		ENSP00000490831.1		A0A1B0GW90

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

120830

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000589

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000133

Gnomad MID

AF:

0.00360

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000109

AC:

AN:

91914

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

50134

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000279

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000174

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000446

AC:

560

AN:

1255004

Hom.:

Cov.:

AF XY:

0.000445

AC XY:

280

AN XY:

628544

show subpopulations

Gnomad4 AFR exome

AF:

0.0000637

Gnomad4 AMR exome

AF:

0.000389

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000302

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000512

Gnomad4 OTH exome

AF:

0.000593

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000372

AC:

AN:

120888

Hom.:

Cov.:

AF XY:

0.000393

AC XY:

AN XY:

58564

show subpopulations

Gnomad4 AFR

AF:

0.0000587

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000133

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000253

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NPIPB7: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.8

DANN

Benign

0.77

DEOGEN2

Benign

0.081

.;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.51

T;T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.067

T;T;T

MetaSVM

Benign

-0.97

PROVEAN

Uncertain

-2.7

.;D;.

REVEL

Benign

0.037

Sift

Benign

0.031

.;D;.

Sift4G

Uncertain

0.024

.;D;D

Vest4

0.067

MutPred

0.51

.;Loss of glycosylation at S255 (P = 0.0235);.;

MVP

0.048

MPC

1.9

ClinPred

0.077

Varity_R

0.16

gMVP

0.0041

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