dbSNP rs770662805: NPIPB5:p.Thr178Asn (chr16-22527961-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001395849.1(NPIPB5):c.533C>A(p.Thr178Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 4)

Failed GnomAD Quality Control

Consequence

NPIPB5
NM_001395849.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.635

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=0.16709936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB5	NM_001395849.1 link	c.533C>A	p.Thr178Asn	missense_variant	Exon 4 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.533C>A	p.Thr178Asn	missense_variant	Exon 4 of 7	1	NM_001395849.1	ENSP00000440703.1		A8MRT5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

12676

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

12676

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

5646

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.9

DANN

Benign

0.97

DEOGEN2

Benign

0.075

.;.;T;T;.;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.00085

LIST_S2

Uncertain

0.87

.;D;D;.;D;.

M_CAP

Benign

0.0049

MetaRNN

Benign

0.17

T;T;T;T;T;T

MetaSVM

Benign

-0.83

PROVEAN

Uncertain

-3.9

D;.;D;D;D;.

REVEL

Benign

0.064

Sift

Uncertain

0.0040

D;.;D;D;D;.

Sift4G

Uncertain

0.0060

D;D;D;D;D;D

Polyphen

1.0

.;.;D;D;.;.

Vest4

0.15, 0.14, 0.14, 0.16

MutPred

0.37

Loss of phosphorylation at T178 (P = 0.0028);Loss of phosphorylation at T178 (P = 0.0028);Loss of phosphorylation at T178 (P = 0.0028);Loss of phosphorylation at T178 (P = 0.0028);Loss of phosphorylation at T178 (P = 0.0028);.;

MVP

0.11

ClinPred

0.75

GERP RS

0.46

Varity_R

0.49

gMVP

0.0076

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over