chr9-32542965-T-G

Variant names:

• chr9-32542965-T-G
• rs61756347
• NM_005802.5:c.1560A>C

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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 Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOPORS NM_005802.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 4 publications found

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]

TOPORS Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 31

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288684 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005802.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPORS	NM_005802.5	MANE Select	c.1560A>C	p.Gln520His	missense	Exon 3 of 3	NP_005793.2
	TOPORS	NM_001195622.2		c.1365A>C	p.Gln455His	missense	Exon 2 of 2	NP_001182551.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPORS	ENST00000360538.7	TSL:1 MANE Select	c.1560A>C	p.Gln520His	missense	Exon 3 of 3	ENSP00000353735.2
	TOPORS	ENST00000379858.1	TSL:1	c.1365A>C	p.Gln455His	missense	Exon 2 of 2	ENSP00000369187.1
	ENSG00000288684	ENST00000681750.1		c.-45+7809A>C		intron	N/A	ENSP00000506413.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-1.5
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.068
Sift	Benign	0.038	D
Sift4G	Benign	0.23	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
Mutation Taster		=91/9	polymorphism

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: rs61756347; hg19: chr9-32542963;