rs1979572

chr17-30184960-G-Achr17-30184960-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032141.4(NSRP1):c.963G>A(p.Gln321=) 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

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 Benign. Variant got -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/exons	MANE	UniProt
NSRP1	NM_032141.4	c.963G>A	p.Gln321=	synonymous_variant	7/7	ENST00000247026.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSRP1	ENST00000247026.10	c.963G>A	p.Gln321=	synonymous_variant	7/7	1	NM_032141.4	P4

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

GnomAD3 exomes AF: 0.520 AC: 130475 AN: 250844 Hom.: 35108 AF XY: 0.516 AC XY: 69992 AN XY: 135560

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 SAS exome AF: 0.527

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

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.583

Gnomad4 ASJ exome AF: 0.551

Gnomad4 EAS exome AF: 0.809

Gnomad4 SAS exome AF: 0.525

Gnomad4 FIN exome AF: 0.445

Gnomad4 NFE exome AF: 0.449

Gnomad4 OTH exome AF: 0.485

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

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.817

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.509

Alfa AF: 0.477 Hom.: 8271

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
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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