Variant chr16-22534038-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001395849.1(NPIPB5):c.1055C>G(p.Pro352Arg) 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 0.00025 ( 0 hom., cov: 15)

Exomes 𝑓: 0.00024 ( 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: -0.198

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039583564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPIPB5	NM_001395849.1 linkuse as main transcript	c.1055C>G	p.Pro352Arg	missense_variant	7/7	ENST00000424340.7
LOC105371131	XR_007065022.1 linkuse as main transcript	n.150+3440G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPIPB5	ENST00000424340.7 linkuse as main transcript	c.1055C>G	p.Pro352Arg	missense_variant	7/7	1	NM_001395849.1	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

123468

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000841

Gnomad ASJ

AF:

0.000651

Gnomad EAS

AF:

0.000289

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000201

Gnomad OTH

AF:

0.000589

GnomAD3 exomes

AF:

0.000127

AC:

AN:

63004

Hom.:

AF XY:

0.0000960

AC XY:

AN XY:

31238

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000894

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00113

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000243

AC:

346

AN:

1425430

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

171

AN XY:

710124

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000905

Gnomad4 ASJ exome

AF:

0.000192

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.00241

Gnomad4 NFE exome

AF:

0.000198

Gnomad4 OTH exome

AF:

0.000202

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000251

AC:

AN:

123596

Hom.:

Cov.:

AF XY:

0.000218

AC XY:

AN XY:

59722

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000839

Gnomad4 ASJ

AF:

0.000651

Gnomad4 EAS

AF:

0.000290

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00190

Gnomad4 NFE

AF:

0.000201

Gnomad4 OTH

AF:

0.000581

Alfa

AF:

0.000491

Hom.:

ExAC

AF:

0.0000233

AC:

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

Aug 10, 2021

The c.1055C>G (p.P352R) alteration is located in exon 7 (coding exon 7) of the NPIPB5 gene. This alteration results from a C to G substitution at nucleotide position 1055, causing the proline (P) at amino acid position 352 to be replaced by an arginine (R). 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

0.39

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.0065

M_CAP

Benign

0.0040

MetaRNN

Benign

0.040

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

N;N

PROVEAN

Pathogenic

-4.7

D;.;D;D;D;.

REVEL

Benign

0.098

Sift

Uncertain

0.0030

D;.;D;D;D;.

Sift4G

Uncertain

0.0070

D;D;D;D;D;D

Polyphen

1.0

.;.;D;D;.;.

Vest4

0.065, 0.10, 0.11, 0.21

MutPred

0.45

Loss of glycosylation at P352 (P = 0.0093);Loss of glycosylation at P352 (P = 0.0093);Loss of glycosylation at P352 (P = 0.0093);Loss of glycosylation at P352 (P = 0.0093);Loss of glycosylation at P352 (P = 0.0093);.;

MVP

0.28

ClinPred

0.22

Varity_R

0.19

gMVP

0.0072

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