Genetic Variant NM_001395849.1:c.1027C>T (chr16-22534010-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_001395849.1(NPIPB5):c.1027C>T(p.Pro343Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 15)

Exomes 𝑓: 0.000030 ( 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: 0.904

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=0.026281863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB5	NM_001395849.1 link	c.1027C>T	p.Pro343Ser	missense_variant	Exon 7 of 7	ENST00000424340.7	NP_001382778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPIPB5	ENST00000424340.7 link	c.1027C>T	p.Pro343Ser	missense_variant	Exon 7 of 7	1	NM_001395849.1	ENSP00000440703.1		A8MRT5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

121104

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000845

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000163

AC:

AN:

61504

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

30408

show subpopulations

Gnomad AFR exome

AF:

0.00153

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000126

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000302

AC:

AN:

1421496

Hom.:

Cov.:

AF XY:

0.0000240

AC XY:

AN XY:

708428

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000337

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000314

AC:

AN:

121104

Hom.:

Cov.:

AF XY:

0.000273

AC XY:

AN XY:

58680

show subpopulations

Gnomad4 AFR

AF:

0.00105

Gnomad4 AMR

AF:

0.0000845

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000253

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1027C>T (p.P343S) alteration is located in exon 7 (coding exon 7) of the NPIPB5 gene. This alteration results from a C to T substitution at nucleotide position 1027, causing the proline (P) at amino acid position 343 to be replaced by a serine (S). 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

0.21

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.3

DANN

Benign

0.48

DEOGEN2

Benign

0.099

.;.;T;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0058

LIST_S2

Benign

0.63

.;T;T;.;T;.

M_CAP

Benign

0.0023

MetaRNN

Benign

0.026

T;T;T;T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Uncertain

-3.0

D;.;D;D;D;.

REVEL

Benign

0.027

Sift

Benign

0.20

T;.;T;T;T;.

Sift4G

Uncertain

0.022

D;T;D;D;D;T

Polyphen

0.018

.;.;B;B;.;.

Vest4

0.065, 0.042, 0.044, 0.063

MutPred

0.47

Loss of catalytic residue at P342 (P = 0.016);Loss of catalytic residue at P342 (P = 0.016);Loss of catalytic residue at P342 (P = 0.016);Loss of catalytic residue at P342 (P = 0.016);Loss of catalytic residue at P342 (P = 0.016);.;

MVP

0.030

ClinPred

0.028

Varity_R

0.073

gMVP

0.0049

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