chr9-32540649-ATAAAG-A

Position:

• chr9-32540649-ATAAAG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005802.5(TOPORS):​c.*733_*737del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 152,784 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (24 hom., cov: 32)
  • Exomes 𝑓: 0.037 (0 hom.)
• Consequence: TOPORS NM_005802.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.531

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-32540649-ATAAAG-A is Benign according to our data. Variant chr9-32540649-ATAAAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 366548.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0142 (2164/152356) while in subpopulation NFE AF= 0.0203 (1381/68032). AF 95% confidence interval is 0.0194. There are 24 homozygotes in gnomad4. There are 1097 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2164 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOPORS	NM_005802.5	c.*733_*737del		3_prime_UTR_variant	3/3	ENST00000360538.7	NP_005793.2
TOPORS	NM_001195622.2	c.*733_*737del		3_prime_UTR_variant	2/2		NP_001182551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOPORS	ENST00000360538.7	c.*733_*737del		3_prime_UTR_variant	3/3	1	NM_005802.5	ENSP00000353735	P3

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2164 AN: 152238 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.00330

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00857

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0379

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.0374 AC: 16 AN: 428 Hom.: 0 AF XY: 0.0433 AC XY: 11 AN XY: 254

Gnomad4 FIN exome AF: 0.0381

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0142 AC: 2164 AN: 152356 Hom.: 24 Cov.: 32 AF XY: 0.0147 AC XY: 1097 AN XY: 74500

Gnomad4 AFR AF: 0.00329

Gnomad4 AMR AF: 0.00856

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0379

Gnomad4 NFE AF: 0.0203

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.0154 Hom.: 4

Bravo AF: 0.0115

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis Pigmentosa, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201977387; hg19: chr9-32540647;