9-32542965-T-G

Position:

• chr9-32542965-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005802.5(TOPORS):​c.1560A>C​(p.Gln520His) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q520Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOPORS NM_005802.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

Genes affected

TOPORS (HGNC:21653): (TOP1 binding arginine/serine rich protein, E3 ubiquitin ligase) This gene encodes a nuclear protein which is serine and arginine rich, and contains a RING-type zinc finger domain. It is highly expressed in the testis, and functions as an ubiquitin-protein E3 ligase. Mutations in this gene are associated with retinitis pigmentosa type 31. Alternatively spliced transcript variants, encoding different isoforms, have been observed for this locus. [provided by RefSeq, Sep 2010]

ENSG00000288684 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04316953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOPORS	NM_005802.5	c.1560A>C	p.Gln520His	missense_variant	3/3	ENST00000360538.7	NP_005793.2
TOPORS	NM_001195622.2	c.1365A>C	p.Gln455His	missense_variant	2/2		NP_001182551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOPORS	ENST00000360538.7	c.1560A>C	p.Gln520His	missense_variant	3/3	1	NM_005802.5	ENSP00000353735.2
TOPORS	ENST00000379858.1	c.1365A>C	p.Gln455His	missense_variant	2/2	1		ENSP00000369187.1
ENSG00000288684	ENST00000681750.1	c.-45+7809A>C		intron_variant				ENSP00000506413.1
ENSG00000288684	ENST00000680198.1	c.198+7809A>C		intron_variant				ENSP00000505143.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.6
DANN	Benign	0.57
DEOGEN2	Benign	0.021	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.068
Sift	Benign	0.038	D;T
Sift4G	Benign	0.23	T;T
Polyphen		0.0	B;.
Vest4		0.13
MutPred		0.13		Gain of relative solvent accessibility (P = 0.1571);.;
MVP		0.27
MPC		0.31
ClinPred		0.049	T
GERP RS		-2.2
Varity_R		0.033
gMVP		0.20

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: rs61756347; hg19: chr9-32542963;