chr9-32552497-C-T

Variant names:

• chr9-32552497-C-T
• rs189362662
• NM_005802.5:c.-61G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005802.5(TOPORS):​c.-61G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,575,322 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00098 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (4 hom.)
• Consequence: TOPORS NM_005802.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.58
• Publications: 1 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]

ENSG00000288684 (HGNC:):

SMIM27 (HGNC:31420): (small integral membrane protein 27) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-32552497-C-T is Benign according to our data. Variant chr9-32552497-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 976633.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000979 (149/152182) while in subpopulation AMR AF = 0.00268 (41/15296). AF 95% confidence interval is 0.00203. There are 1 homozygotes in GnomAd4. There are 86 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4 AD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPORS	NM_005802.5	MANE Select	c.-61G>A		5_prime_UTR	Exon 1 of 3	NP_005793.2
	SMIM27	NM_001387564.1	MANE Select	c.45+18C>T		intron	N/A	NP_001374493.1	A0A1B0GUW7
	TOPORS	NM_001195622.2		c.-61G>A		5_prime_UTR	Exon 1 of 2	NP_001182551.1	Q9NS56-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPORS	ENST00000360538.7	TSL:1 MANE Select	c.-61G>A		5_prime_UTR	Exon 1 of 3	ENSP00000353735.2	Q9NS56-1
	TOPORS	ENST00000379858.1	TSL:1	c.-61G>A		5_prime_UTR	Exon 1 of 2	ENSP00000369187.1	Q9NS56-2
	ENSG00000288684	ENST00000681750.1		c.-408G>A		5_prime_UTR	Exon 1 of 20	ENSP00000506413.1	A0A7P0TB70

Frequencies

GnomAD3 genomes AF: 0.000986 AC: 150 AN: 152064 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.00480

GnomAD2 exomes AF: 0.00107 AC: 197 AN: 183652 AF XY: 0.00110

Gnomad AFR exome AF: 0.000301

Gnomad AMR exome AF: 0.00120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000237

Gnomad NFE exome AF: 0.00162

Gnomad OTH exome AF: 0.00183

GnomAD4 exome AF: 0.00119 AC: 1695 AN: 1423140 Hom.: 4 Cov.: 31 AF XY: 0.00117 AC XY: 827 AN XY: 704642

African (AFR) AF: 0.000183 AC: 6 AN: 32758

American (AMR) AF: 0.00166 AC: 65 AN: 39042

Ashkenazi Jewish (ASJ) AF: 0.0000391 AC: 1 AN: 25574

East Asian (EAS) AF: 0.00 AC: 0 AN: 38058

South Asian (SAS) AF: 0.000804 AC: 66 AN: 82078

European-Finnish (FIN) AF: 0.000542 AC: 27 AN: 49836

Middle Eastern (MID) AF: 0.000229 AC: 1 AN: 4370

European-Non Finnish (NFE) AF: 0.00132 AC: 1447 AN: 1092660

Other (OTH) AF: 0.00140 AC: 82 AN: 58764

GnomAD4 genome AF: 0.000979 AC: 149 AN: 152182 Hom.: 1 Cov.: 33 AF XY: 0.00116 AC XY: 86 AN XY: 74394

African (AFR) AF: 0.000313 AC: 13 AN: 41524

American (AMR) AF: 0.00268 AC: 41 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000832 AC: 4 AN: 4810

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00113 AC: 77 AN: 67980

Other (OTH) AF: 0.00475 AC: 10 AN: 2104

Alfa AF: 0.00136 Hom.: 0

Bravo AF: 0.00125

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.89
PhyloP100		-2.6
PromoterAI		0.0078	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs189362662; hg19: chr9-32552495;