rs1979572

Variant names:

• chr17-30184960-G-A
• rs1979572
• NM_032141.4:c.963G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-30184960-G-A
• chr17-30184960-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 31 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032141.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSRP1	NM_032141.4	MANE Select	c.963G>A	p.Gln321Gln	synonymous	Exon 7 of 7	NP_115517.1
	NSRP1	NM_001261467.2		c.801G>A	p.Gln267Gln	synonymous	Exon 6 of 6	NP_001248396.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSRP1	ENST00000247026.10	TSL:1 MANE Select	c.963G>A	p.Gln321Gln	synonymous	Exon 7 of 7	ENSP00000247026.5
	NSRP1	ENST00000612959.4	TSL:1	c.801G>A	p.Gln267Gln	synonymous	Exon 6 of 6	ENSP00000477862.1
	NSRP1	ENST00000394826.8	TSL:1	n.*839G>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000378303.4

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75337 AN: 151716 Hom.: 19255 Cov.: 30

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

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.: 61 AF XY: 0.474 AC XY: 344356 AN XY: 727142

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

GnomAD4 genome AF: 0.496 AC: 75366 AN: 151834 Hom.: 19261 Cov.: 30 AF XY: 0.501 AC XY: 37190 AN XY: 74192

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.76
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)

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

Other links and lift over

dbSNP: rs1979572; hg19: chr17-28511978; COSMIC: COSV55933486; COSMIC: COSV55933486;