Variant 16-22534050-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001395849.1(NPIPB5):c.1067C>A(p.Pro356His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 15)

Exomes 𝑓: 0.00012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NPIPB5
NM_001395849.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.894

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11440173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPIPB5	NM_001395849.1 linkuse as main transcript	c.1067C>A	p.Pro356His	missense_variant	7/7	ENST00000424340.7	NP_001382778.1
LOC105371131	XR_007065022.1 linkuse as main transcript	n.150+3428G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPIPB5	ENST00000424340.7 linkuse as main transcript	c.1067C>A	p.Pro356His	missense_variant	7/7	1	NM_001395849.1	ENSP00000440703	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

117190

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000343

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000710

Gnomad ASJ

AF:

0.000726

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000968

Gnomad OTH

AF:

0.000639

GnomAD3 exomes

AF:

0.000302

AC:

AN:

59550

Hom.:

AF XY:

0.000368

AC XY:

AN XY:

29912

show subpopulations

Gnomad AFR exome

AF:

0.000355

Gnomad AMR exome

AF:

0.000988

Gnomad ASJ exome

AF:

0.000584

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000128

Gnomad OTH exome

AF:

0.000502

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000115

AC:

162

AN:

1408130

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

700946

show subpopulations

Gnomad4 AFR exome

AF:

0.000361

Gnomad4 AMR exome

AF:

0.000616

Gnomad4 ASJ exome

AF:

0.000519

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000851

Gnomad4 OTH exome

AF:

0.000222

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000239

AC:

AN:

117322

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

56810

show subpopulations

Gnomad4 AFR

AF:

0.000342

Gnomad4 AMR

AF:

0.000709

Gnomad4 ASJ

AF:

0.000726

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000968

Gnomad4 OTH

AF:

0.000631

Alfa

AF:

0.000169

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.1067C>A (p.P356H) alteration is located in exon 7 (coding exon 7) of the NPIPB5 gene. This alteration results from a C to A substitution at nucleotide position 1067, causing the proline (P) at amino acid position 356 to be replaced by a histidine (H). 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

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.074

.;.;T;T;.;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.41

.;T;T;.;T;.

M_CAP

Benign

0.0053

MetaRNN

Benign

0.11

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N

PROVEAN

Uncertain

-2.9

D;.;D;D;D;.

REVEL

Benign

0.065

Sift

Uncertain

0.0020

D;.;D;D;D;.

Sift4G

Uncertain

0.0080

D;D;D;D;D;D

Polyphen

1.0

.;.;D;D;.;.

Vest4

0.14, 0.085, 0.11, 0.20

MutPred

0.31

Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);.;

MVP

0.17

ClinPred

0.073

Varity_R

0.26

gMVP

0.011

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