Variant 16-22534019-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 ENST00000424340.7(NPIPB5):c.1036C>G(p.Leu346Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 15)

Exomes 𝑓: 0.000040 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NPIPB5
ENST00000424340.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.206

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=0.022234142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPIPB5	NM_001395849.1 linkuse as main transcript	c.1036C>G	p.Leu346Val	missense_variant	7/7	ENST00000424340.7	NP_001382778.1
LOC105371131	XR_007065022.1 linkuse as main transcript	n.150+3459G>C		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.1036C>G	p.Leu346Val	missense_variant	7/7	1	NM_001395849.1	ENSP00000440703	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

116402

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000320

Gnomad AMI

AF:

0.00163

Gnomad AMR

AF:

0.000352

Gnomad ASJ

AF:

0.000699

Gnomad EAS

AF:

0.000304

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00111

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.000620

GnomAD3 exomes

AF:

0.0000645

AC:

AN:

62054

Hom.:

AF XY:

0.0000326

AC XY:

AN XY:

30662

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000181

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000125

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000389

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000397

AC:

AN:

1410562

Hom.:

Cov.:

AF XY:

0.0000398

AC XY:

AN XY:

703338

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000681

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000731

Gnomad4 NFE exome

AF:

0.0000417

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000515

AC:

AN:

116510

Hom.:

Cov.:

AF XY:

0.000530

AC XY:

AN XY:

56588

show subpopulations

Gnomad4 AFR

AF:

0.000320

Gnomad4 AMR

AF:

0.000351

Gnomad4 ASJ

AF:

0.000699

Gnomad4 EAS

AF:

0.000304

Gnomad4 SAS

AF:

0.000289

Gnomad4 FIN

AF:

0.00111

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.000613

Alfa

AF:

0.000797

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 24, 2023

The c.1036C>G (p.L346V) 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 1036, causing the leucine (L) at amino acid position 346 to be replaced by a valine (V). 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

Benign

0.27

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.7

DANN

Benign

0.40

DEOGEN2

Benign

0.056

.;.;T;T;.;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.40

.;T;T;.;T;.

M_CAP

Benign

0.0026

MetaRNN

Benign

0.022

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-1.3

N;.;N;N;N;.

REVEL

Benign

0.081

Sift

Benign

0.24

T;.;T;T;T;.

Sift4G

Benign

0.24

T;T;T;T;T;T

Polyphen

0.33

.;.;B;B;.;.

Vest4

0.065, 0.054, 0.059, 0.10

MutPred

0.39

Loss of catalytic residue at L346 (P = 0.0226);Loss of catalytic residue at L346 (P = 0.0226);Loss of catalytic residue at L346 (P = 0.0226);Loss of catalytic residue at L346 (P = 0.0226);Loss of catalytic residue at L346 (P = 0.0226);.;

MVP

0.014

ClinPred

0.046

Varity_R

0.099

gMVP

0.0023

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