17-30178149-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_032141.4(NSRP1):c.250A>G(p.Lys84Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0029 in 1,607,860 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (10 hom.)
• Consequence: NSRP1 NM_032141.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.92

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010900557).
• BP6: Variant 17-30178149-A-G is Benign according to our data. Variant chr17-30178149-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3052334.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSRP1	NM_032141.4	c.250A>G	p.Lys84Glu	missense_variant	4/7	ENST00000247026.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSRP1	ENST00000247026.10	c.250A>G	p.Lys84Glu	missense_variant	4/7	1	NM_032141.4	P4

Frequencies

GnomAD3 genomes AF: 0.00184 AC: 280 AN: 152056 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00318

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00172 AC: 418 AN: 242392 Hom.: 0 AF XY: 0.00187 AC XY: 245 AN XY: 131018

Gnomad AFR exome AF: 0.000696

Gnomad AMR exome AF: 0.000778

Gnomad ASJ exome AF: 0.00203

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000247

Gnomad FIN exome AF: 0.000372

Gnomad NFE exome AF: 0.00299

Gnomad OTH exome AF: 0.00239

GnomAD4 exome AF: 0.00301 AC: 4381 AN: 1455686 Hom.: 10 Cov.: 31 AF XY: 0.00298 AC XY: 2159 AN XY: 723758

Gnomad4 AFR exome AF: 0.000482

Gnomad4 AMR exome AF: 0.000825

Gnomad4 ASJ exome AF: 0.00242

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000190

Gnomad4 FIN exome AF: 0.000225

Gnomad4 NFE exome AF: 0.00365

Gnomad4 OTH exome AF: 0.00302

GnomAD4 genome AF: 0.00184 AC: 280 AN: 152174 Hom.: 1 Cov.: 32 AF XY: 0.00160 AC XY: 119 AN XY: 74406

Gnomad4 AFR AF: 0.000578

Gnomad4 AMR AF: 0.00177

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00318

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00247 Hom.: 0

Bravo AF: 0.00204

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00363 AC: 14

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00256 AC: 22

ExAC AF: 0.00187 AC: 227

EpiCase AF: 0.00331

EpiControl AF: 0.00283

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

NSRP1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 18, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.37
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.069	T;T;T;T;T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	D;D;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.011	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L;.;.;.;.
MutationTaster	Benign	0.80	D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.7	N;.;.;.;.
REVEL	Benign	0.081
Sift	Benign	0.15	T;.;.;.;.
Sift4G	Benign	0.17	T;T;T;T;T
Polyphen		0.87	P;.;.;.;.
Vest4		0.39
MVP		0.44
MPC		0.16
ClinPred		0.021	T
GERP RS		3.8
Varity_R		0.20
gMVP		0.065

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

Other links and lift over

dbSNP: rs143842750; hg19: chr17-28505167;