15-41349099-A-G

Position:

• chr15-41349099-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016359.5(NUSAP1):​c.164A>G​(p.Asp55Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUSAP1 NM_016359.5 missense, splice_region
• Scores: Splicing: ADA: 0.00003085
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.181

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090651155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUSAP1	NM_016359.5	c.164A>G	p.Asp55Gly	missense_variant, splice_region_variant	3/11	ENST00000559596.6	NP_057443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUSAP1	ENST00000559596.6	c.164A>G	p.Asp55Gly	missense_variant, splice_region_variant	3/11	1	NM_016359.5	ENSP00000453403	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

The c.164A>G (p.D55G) alteration is located in exon 3 (coding exon 3) of the NUSAP1 gene. This alteration results from a A to G substitution at nucleotide position 164, causing the aspartic acid (D) at amino acid position 55 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.35	.;.;T;.;.;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.68	T;T;T;T;T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.091	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	2.0	M;.;M;M;M;M
MutationTaster	Benign	0.57	D;D;D;D;D;D;N
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.1	D;N;D;D;D;D
REVEL	Benign	0.068
Sift	Benign	0.096	T;D;T;T;T;T
Sift4G	Benign	0.25	T;T;T;T;T;T
Polyphen		0.82, 0.65, 0.81	.;.;P;P;P;P
Vest4		0.17
MutPred		0.17		Gain of MoRF binding (P = 0.1185);.;Gain of MoRF binding (P = 0.1185);Gain of MoRF binding (P = 0.1185);Gain of MoRF binding (P = 0.1185);Gain of MoRF binding (P = 0.1185);
MVP		0.30
MPC		0.051
ClinPred		0.41	T
GERP RS		-0.73
Varity_R		0.097
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000031
dbscSNV1_RF	Benign	0.11
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-41641297;