chr9-32541717-T-G

Variant names:

• chr9-32541717-T-G
• rs193920910
• NM_005802.5:c.2808A>C

Variant summary

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

The NM_005802.5(TOPORS):​c.2808A>C​(p.Gln936His) 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. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOPORS NM_005802.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.354

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=0.061683953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOPORS	NM_005802.5	c.2808A>C	p.Gln936His	missense_variant	Exon 3 of 3	ENST00000360538.7	NP_005793.2
TOPORS	NM_001195622.2	c.2613A>C	p.Gln871His	missense_variant	Exon 2 of 2		NP_001182551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOPORS	ENST00000360538.7	c.2808A>C	p.Gln936His	missense_variant	Exon 3 of 3	1	NM_005802.5	ENSP00000353735.2
TOPORS	ENST00000379858.1	c.2613A>C	p.Gln871His	missense_variant	Exon 2 of 2	1		ENSP00000369187.1
ENSG00000288684	ENST00000681750.1	c.-45+9057A>C		intron_variant	Intron 3 of 19			ENSP00000506413.1
ENSG00000288684	ENST00000680198.1	c.198+9057A>C		intron_variant	Intron 2 of 18			ENSP00000505143.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

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Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.4
DANN	Benign	0.93
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.64	N;N
REVEL	Benign	0.072
Sift	Benign	0.11	T;T
Sift4G	Uncertain	0.042	D;T
Polyphen		0.0	B;.
Vest4		0.062
MutPred		0.15		Gain of catalytic residue at N937 (P = 0.0584);.;
MVP		0.38
MPC		0.29
ClinPred		0.036	T
GERP RS		-1.3
Varity_R		0.043
gMVP		0.15

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: rs193920910; hg19: chr9-32541715; COSMIC: COSV62117876;