dbSNP rs1979572: NSRP1:p.Gln321Gln (chr17-30184960-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_032141.4(NSRP1):c.963G>A(p.Gln321Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,613,576 control chromosomes in the GnomAD database, including 186,586 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.50 ( 19261 hom., cov: 30)

Exomes 𝑓: 0.47 ( 167325 hom. )

Consequence

NSRP1
NM_032141.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.423

Publications

31 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with spasticity, seizures, and brain abnormalities
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

NSRP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP7

Synonymous conserved (PhyloP=-0.423 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSRP1	NM_032141.4 link	c.963G>A	p.Gln321Gln	synonymous_variant	Exon 7 of 7	ENST00000247026.10	NP_115517.1	Q9H0G5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSRP1	ENST00000247026.10 link	c.963G>A	p.Gln321Gln	synonymous_variant	Exon 7 of 7	1	NM_032141.4	ENSP00000247026.5		Q9H0G5

Frequencies

GnomAD3 genomes

AF:

0.497

AC:

75337

AN:

151716

Hom.:

19255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.513

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.541

Gnomad ASJ

AF:

0.559

Gnomad EAS

AF:

0.816

Gnomad SAS

AF:

0.535

Gnomad FIN

AF:

0.438

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.455

Gnomad OTH

AF:

0.514

GnomAD2 exomes

AF:

0.520

AC:

130475

AN:

250844

AF XY:

0.516

show subpopulations

Gnomad AFR exome

AF:

0.513

Gnomad AMR exome

AF:

0.590

Gnomad ASJ exome

AF:

0.559

Gnomad EAS exome

AF:

0.805

Gnomad FIN exome

AF:

0.451

Gnomad NFE exome

AF:

0.463

Gnomad OTH exome

AF:

0.501

GnomAD4 exome

AF:

0.473

AC:

690754

AN:

1461742

Hom.:

167325

Cov.:

AF XY:

0.474

AC XY:

344356

AN XY:

727142

show subpopulations

African (AFR)

AF:

0.520

AC:

17418

AN:

33478

American (AMR)

AF:

0.583

AC:

26070

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.551

AC:

14388

AN:

26134

East Asian (EAS)

AF:

0.809

AC:

32120

AN:

39700

South Asian (SAS)

AF:

0.525

AC:

45257

AN:

86246

European-Finnish (FIN)

AF:

0.445

AC:

23742

AN:

53412

Middle Eastern (MID)

AF:

0.525

AC:

3028

AN:

5768

European-Non Finnish (NFE)

AF:

0.449

AC:

499461

AN:

1111918

Other (OTH)

AF:

0.485

AC:

29270

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

21693

43386

65080

86773

108466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15186

30372

45558

60744

75930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.496

AC:

75366

AN:

151834

Hom.:

19261

Cov.:

AF XY:

0.501

AC XY:

37190

AN XY:

74192

show subpopulations

African (AFR)

AF:

0.513

AC:

21220

AN:

41352

American (AMR)

AF:

0.541

AC:

8241

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.559

AC:

1940

AN:

3468

East Asian (EAS)

AF:

0.817

AC:

4218

AN:

5164

South Asian (SAS)

AF:

0.534

AC:

2569

AN:

4812

European-Finnish (FIN)

AF:

0.438

AC:

4620

AN:

10544

Middle Eastern (MID)

AF:

0.517

AC:

151

AN:

292

European-Non Finnish (NFE)

AF:

0.455

AC:

30905

AN:

67940

Other (OTH)

AF:

0.509

AC:

1077

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1858

3717

5575

7434

9292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

676

1352

2028

2704

3380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.478

Hom.:

8376

Bravo

AF:

0.508

Asia WGS

AF:

0.608

AC:

2116

AN:

3478

EpiCase

AF:

0.453

EpiControl

AF:

0.461

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.76

(source)

DANN

Benign

0.58

PhyloP100

-0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over