Variant 16-29383124-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001310137.5(NPIPB11):c.1808C>G(p.Pro603Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,569,374 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 4 hom., cov: 22)

Exomes 𝑓: 0.0024 ( 36 hom. )

Consequence

NPIPB11
NM_001310137.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.123

Variant links:

Genes affected

NPIPB11 (HGNC:37453): (nuclear pore complex interacting protein family member B11) Predicted to act upstream of or within prevention of polyspermy. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NPIPB11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004241675).

BP6

Variant 16-29383124-G-C is Benign according to our data. Variant chr16-29383124-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2646360.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NPIPB11	NM_001310137.5 linkuse as main transcript	c.1808C>G	p.Pro603Arg	missense_variant	8/8	ENST00000698511.1	NP_001297066.2
NPIPB11	XM_047434576.1 linkuse as main transcript	c.1808C>G	p.Pro603Arg	missense_variant	7/8		XP_047290532.1
NPIPB11	XM_047434577.1 linkuse as main transcript	c.1442C>G	p.Pro481Arg	missense_variant	8/9		XP_047290533.1
NPIPB11	XM_047434578.1 linkuse as main transcript	c.1385C>G	p.Pro462Arg	missense_variant	8/9		XP_047290534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPIPB11	ENST00000698511.1 linkuse as main transcript	c.1808C>G	p.Pro603Arg	missense_variant	8/8		NM_001310137.5	ENSP00000513761	P1
NPIPB11	ENST00000524087.5 linkuse as main transcript	c.1808C>G	p.Pro603Arg	missense_variant	8/8	5		ENSP00000430853	P1

Frequencies

GnomAD3 genomes

AF:

0.00554

AC:

760

AN:

137220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00579

Gnomad ASJ

AF:

0.000614

Gnomad EAS

AF:

0.000222

Gnomad SAS

AF:

0.000722

Gnomad FIN

AF:

0.00425

Gnomad MID

AF:

0.00847

Gnomad NFE

AF:

0.00866

Gnomad OTH

AF:

0.00890

GnomAD3 exomes

AF:

0.00208

AC:

508

AN:

244338

Hom.:

AF XY:

0.00186

AC XY:

248

AN XY:

133176

show subpopulations

Gnomad AFR exome

AF:

0.000903

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00236

Gnomad NFE exome

AF:

0.00314

Gnomad OTH exome

AF:

0.00335

GnomAD4 exome

AF:

0.00245

AC:

3507

AN:

1432048

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

1814

AN XY:

712920

show subpopulations

Gnomad4 AFR exome

AF:

0.000652

Gnomad4 AMR exome

AF:

0.00227

Gnomad4 ASJ exome

AF:

0.000310

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000305

Gnomad4 FIN exome

AF:

0.00351

Gnomad4 NFE exome

AF:

0.00273

Gnomad4 OTH exome

AF:

0.00324

GnomAD4 genome

AF:

0.00553

AC:

760

AN:

137326

Hom.:

Cov.:

AF XY:

0.00529

AC XY:

355

AN XY:

67112

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00579

Gnomad4 ASJ

AF:

0.000614

Gnomad4 EAS

AF:

0.000222

Gnomad4 SAS

AF:

0.000722

Gnomad4 FIN

AF:

0.00425

Gnomad4 NFE

AF:

0.00866

Gnomad4 OTH

AF:

0.00885

Alfa

AF:

0.00207

Hom.:

ExAC

AF:

0.00479

AC:

577

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

NPIPB11: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0084

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.43

M_CAP

Benign

0.0022

MetaRNN

Benign

0.0042

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-0.73

REVEL

Benign

0.017

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0020

Vest4

0.13

MutPred

0.27

Gain of MoRF binding (P = 0.0087);

MVP

0.17

ClinPred

0.0042

Varity_R

0.087

gMVP

0.0057

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