rs7168431

Positions:

• chr15-41380186-A-G

Variant summary

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

The NM_016359.5(NUSAP1):​c.1326A>G​(p.Ter442=) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,554,700 control chromosomes in the GnomAD database, including 46,136 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 0.18 (3372 hom., cov: 31)
  • Exomes 𝑓: 0.24 (42764 hom.)
• Consequence: NUSAP1 NM_016359.5 stop_retained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

Genes affected

NUSAP1 (HGNC:18538): (nucleolar and spindle associated protein 1) NUSAP1 is a nucleolar-spindle-associated protein that plays a role in spindle microtubule organization (Raemaekers et al., 2003 [PubMed 12963707]).[supplied by OMIM, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=1.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUSAP1	NM_016359.5	c.1326A>G	p.Ter442=	stop_retained_variant	11/11	ENST00000559596.6	NP_057443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUSAP1	ENST00000559596.6	c.1326A>G	p.Ter442=	stop_retained_variant	11/11	1	NM_016359.5	ENSP00000453403	P4

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28058 AN: 151770 Hom.: 3374 Cov.: 31

Gnomad AFR AF: 0.0488

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.192

GnomAD3 exomes AF: 0.209 AC: 35540 AN: 170256 Hom.: 4365 AF XY: 0.212 AC XY: 19110 AN XY: 90184

Gnomad AFR exome AF: 0.0447

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.0142

Gnomad SAS exome AF: 0.190

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.234

GnomAD4 exome AF: 0.239 AC: 335027 AN: 1402812 Hom.: 42764 Cov.: 28 AF XY: 0.238 AC XY: 165178 AN XY: 693224

Gnomad4 AFR exome AF: 0.0429

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.0153

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.185 AC: 28049 AN: 151888 Hom.: 3372 Cov.: 31 AF XY: 0.186 AC XY: 13797 AN XY: 74170

Gnomad4 AFR AF: 0.0487

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.0149

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.192

Alfa AF: 0.242 Hom.: 7457

Bravo AF: 0.171

Asia WGS AF: 0.124 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.8
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: rs7168431; hg19: chr15-41672384; COSMIC: COSV52970610; COSMIC: COSV52970610;