chr9-32541024-CAA-C

Variant names:

• chr9-32541024-CAA-C
• rs34721491
• NM_005802.5:c.*361_*362delTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_005802.5(TOPORS):​c.*361_*362delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 164,610 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 20)
  • Exomes 𝑓: 0.00095 (0 hom.)
• Consequence: TOPORS NM_005802.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000951 (18/18936) while in subpopulation NFE AF= 0.00141 (15/10672). AF 95% confidence interval is 0.000866. There are 0 homozygotes in gnomad4_exome. There are 10 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOPORS	NM_005802.5	c.*361_*362delTT		3_prime_UTR_variant	Exon 3 of 3	ENST00000360538.7	NP_005793.2
TOPORS	NM_001195622.2	c.*361_*362delTT		3_prime_UTR_variant	Exon 2 of 2		NP_001182551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOPORS	ENST00000360538	c.*361_*362delTT		3_prime_UTR_variant	Exon 3 of 3	1	NM_005802.5	ENSP00000353735.2
TOPORS	ENST00000379858	c.*361_*362delTT		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000369187.1
ENSG00000288684	ENST00000681750.1	c.-45+9748_-45+9749delTT		intron_variant	Intron 3 of 19			ENSP00000506413.1
ENSG00000288684	ENST00000680198.1	c.198+9748_198+9749delTT		intron_variant	Intron 2 of 18			ENSP00000505143.1

Frequencies

GnomAD3 genomes AF: 0.00000686 AC: 1 AN: 145674 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000110

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000951 AC: 18 AN: 18936 Hom.: 0 AF XY: 0.000978 AC XY: 10 AN XY: 10228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00357

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000701

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00141

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000686 AC: 1 AN: 145674 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 70624

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000110

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs34721491; hg19: chr9-32541022;