Variant 17-30184776-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032141.4(NSRP1):c.779T>C(p.Ile260Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

NSRP1
NM_032141.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.07

Variant links:

Genes affected

NSRP1 (HGNC:25305): (nuclear speckle splicing regulatory protein 1) Enables mRNA binding activity. Involved in developmental process and regulation of alternative mRNA splicing, via spliceosome. Located in nuclear speck. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

NSRP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02534011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSRP1	NM_032141.4 linkuse as main transcript	c.779T>C	p.Ile260Thr	missense_variant	7/7	ENST00000247026.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSRP1	ENST00000247026.10 linkuse as main transcript	c.779T>C	p.Ile260Thr	missense_variant	7/7	1	NM_032141.4	P4

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151848

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251010

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461732

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151848

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74148

show subpopulations

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Jan 17, 2024

The c.779T>C (p.I260T) alteration is located in exon 7 (coding exon 7) of the NSRP1 gene. This alteration results from a T to C substitution at nucleotide position 779, causing the isoleucine (I) at amino acid position 260 to be replaced by a threonine (T). 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

0.058

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.72

Cadd

Benign

0.79

Dann

Benign

0.48

DEOGEN2

Benign

0.025

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.36

T;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.025

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

0.83

N;.

REVEL

Benign

0.0040

Sift

Benign

0.17

T;.

Sift4G

Benign

0.61

T;T

Polyphen

0.010

B;.

Vest4

0.027

MutPred

0.16

Loss of stability (P = 0.0351);.;

MVP

0.11

MPC

0.11

ClinPred

0.037

GERP RS

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.019

gMVP

0.020

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