Variant 16-22534094-G-A 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.1111G>A(p.Glu371Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 9)

Exomes 𝑓: 0.00025 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

NPIPB5
NM_001395849.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.160

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=0.0329749).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPIPB5	NM_001395849.1 linkuse as main transcript	c.1111G>A	p.Glu371Lys	missense_variant	7/7	ENST00000424340.7
LOC105371131	XR_007065022.1 linkuse as main transcript	n.150+3384C>T		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.1111G>A	p.Glu371Lys	missense_variant	7/7	1	NM_001395849.1	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

72312

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000501

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000402

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000255

AC:

AN:

58790

Hom.:

AF XY:

0.000234

AC XY:

AN XY:

29902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000893

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000253

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00106

Gnomad NFE exome

AF:

0.000441

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000253

AC:

264

AN:

1044094

Hom.:

Cov.:

AF XY:

0.000298

AC XY:

159

AN XY:

533766

show subpopulations

Gnomad4 AFR exome

AF:

0.0000340

Gnomad4 AMR exome

AF:

0.0000769

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000269

Gnomad4 SAS exome

AF:

0.0000508

Gnomad4 FIN exome

AF:

0.0000270

Gnomad4 NFE exome

AF:

0.000318

Gnomad4 OTH exome

AF:

0.000231

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000207

AC:

AN:

72384

Hom.:

Cov.:

AF XY:

0.000315

AC XY:

AN XY:

34964

show subpopulations

Gnomad4 AFR

AF:

0.0000457

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000502

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000402

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000742

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

Dec 13, 2023

The c.1111G>A (p.E371K) alteration is located in exon 7 (coding exon 7) of the NPIPB5 gene. This alteration results from a G to A substitution at nucleotide position 1111, causing the glutamic acid (E) at amino acid position 371 to be replaced by a lysine (K). 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

-0.24

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.024

M_CAP

Benign

0.0022

MetaRNN

Benign

0.033

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-0.64

N;.;N;N;N;.

REVEL

Benign

0.043

Sift

Benign

0.14

T;.;T;T;T;.

Sift4G

Benign

0.45

T;T;T;T;T;T

Polyphen

0.34

.;.;B;B;.;.

Vest4

0.094, 0.087, 0.073

MutPred

0.28

Gain of methylation at E371 (P = 0.0037);Gain of methylation at E371 (P = 0.0037);Gain of methylation at E371 (P = 0.0037);Gain of methylation at E371 (P = 0.0037);Gain of methylation at E371 (P = 0.0037);.;

MVP

0.014

ClinPred

0.039

Varity_R

0.11

gMVP

0.012

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