Genetic Variant NPIPB11:p.Ser477Ser (chr16-29383501-A-G) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001310137.5(NPIPB11):c.1431T>C(p.Ser477Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 9)

Exomes 𝑓: 0.0012 ( 232 hom. )

Failed GnomAD Quality Control

Consequence

NPIPB11
NM_001310137.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.47

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.07).

BP6

Variant 16-29383501-A-G is Benign according to our data. Variant chr16-29383501-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2646361.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.47 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
NPIPB11	NM_001310137.5 link	c.1431T>C	p.Ser477Ser	synonymous_variant	Exon 8 of 8	ENST00000698511.1	NP_001297066.2
NPIPB11	XM_047434576.1 link	c.1431T>C	p.Ser477Ser	synonymous_variant	Exon 7 of 8		XP_047290532.1
NPIPB11	XM_047434577.1 link	c.1086-21T>C		intron_variant	Intron 7 of 8		XP_047290533.1
NPIPB11	XM_047434578.1 link	c.1029-21T>C		intron_variant	Intron 7 of 8		XP_047290534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPIPB11	ENST00000698511.1 link	c.1431T>C	p.Ser477Ser	synonymous_variant	Exon 8 of 8		NM_001310137.5	ENSP00000513761.1		E5RHQ5
NPIPB11	ENST00000524087.5 link	c.1431T>C	p.Ser477Ser	synonymous_variant	Exon 8 of 8	5		ENSP00000430853.1		E5RHQ5

Frequencies

GnomAD3 genomes

AF:

0.000384

AC:

AN:

65060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000179

Gnomad ASJ

AF:

0.000566

Gnomad EAS

AF:

0.00364

Gnomad SAS

AF:

0.000906

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000494

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00235

AC:

453

AN:

192582

Hom.:

AF XY:

0.00220

AC XY:

234

AN XY:

106222

show subpopulations

Gnomad AFR exome

AF:

0.000998

Gnomad AMR exome

AF:

0.00348

Gnomad ASJ exome

AF:

0.00440

Gnomad EAS exome

AF:

0.00229

Gnomad SAS exome

AF:

0.00139

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.00226

Gnomad OTH exome

AF:

0.00580

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00117

AC:

1389

AN:

1186790

Hom.:

232

Cov.:

AF XY:

0.00127

AC XY:

753

AN XY:

592172

show subpopulations

Gnomad4 AFR exome

AF:

0.000391

Gnomad4 AMR exome

AF:

0.00167

Gnomad4 ASJ exome

AF:

0.00344

Gnomad4 EAS exome

AF:

0.000677

Gnomad4 SAS exome

AF:

0.00250

Gnomad4 FIN exome

AF:

0.00316

Gnomad4 NFE exome

AF:

0.000941

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.000384

AC:

AN:

65098

Hom.:

Cov.:

AF XY:

0.000425

AC XY:

AN XY:

30590

show subpopulations

Gnomad4 AFR

AF:

0.000118

Gnomad4 AMR

AF:

0.000179

Gnomad4 ASJ

AF:

0.000566

Gnomad4 EAS

AF:

0.00365

Gnomad4 SAS

AF:

0.000916

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000494

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NPIPB11: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

3.8

DANN

Benign

0.27

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