rs7168431

Variant names:

• chr15-41380186-A-G
• rs7168431
• NM_016359.5:c.1326A>G

Variant summary

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

The NM_016359.5(NUSAP1):​c.1326A>G​(p.Ter442Ter) 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
• Publications: 29 publications found

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]

ENSG00000285920 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016359.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUSAP1	NM_016359.5	MANE Select	c.1326A>G	p.Ter442Ter	stop_retained	Exon 11 of 11	NP_057443.2	Q9BXS6-1
	NUSAP1	NM_001301136.2		c.1323A>G	p.Ter441Ter	stop_retained	Exon 11 of 11	NP_001288065.1	Q9BXS6-5
	NUSAP1	NM_018454.8		c.1323A>G	p.Ter441Ter	stop_retained	Exon 11 of 11	NP_060924.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUSAP1	ENST00000559596.6	TSL:1 MANE Select	c.1326A>G	p.Ter442Ter	stop_retained	Exon 11 of 11	ENSP00000453403.1	Q9BXS6-1
	ENSG00000285920	ENST00000661438.1		c.1326A>G	p.Ter442Ter	stop_retained	Exon 12 of 12	ENSP00000499503.1
	NUSAP1	ENST00000414849.6	TSL:1	c.1323A>G	p.Ter441Ter	stop_retained	Exon 11 of 11	ENSP00000400746.2	Q9BXS6-2

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

GnomAD2 exomes AF: 0.209 AC: 35540 AN: 170256 AF XY: 0.212

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 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

African (AFR) AF: 0.0429 AC: 1366 AN: 31818

American (AMR) AF: 0.140 AC: 5016 AN: 35938

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 6522 AN: 25106

East Asian (EAS) AF: 0.0153 AC: 563 AN: 36902

South Asian (SAS) AF: 0.190 AC: 15004 AN: 78858

European-Finnish (FIN) AF: 0.299 AC: 15048 AN: 50400

Middle Eastern (MID) AF: 0.225 AC: 1277 AN: 5682

European-Non Finnish (NFE) AF: 0.257 AC: 277253 AN: 1079664

Other (OTH) AF: 0.222 AC: 12978 AN: 58444

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

African (AFR) AF: 0.0487 AC: 2020 AN: 41518

American (AMR) AF: 0.178 AC: 2716 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 895 AN: 3468

East Asian (EAS) AF: 0.0149 AC: 77 AN: 5178

South Asian (SAS) AF: 0.177 AC: 854 AN: 4812

European-Finnish (FIN) AF: 0.300 AC: 3124 AN: 10424

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17599 AN: 67948

Other (OTH) AF: 0.192 AC: 405 AN: 2110

Alfa AF: 0.233 Hom.: 9412

Bravo AF: 0.171

Asia WGS AF: 0.124 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.8
DANN	Benign	0.58
PhyloP100		1.0
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: rs7168431; hg19: chr15-41672384; COSMIC: COSV52970610; COSMIC: COSV52970610;