9-32551161-C-A

Variant names:

• chr9-32551161-C-A
• rs549299723
• NM_005802.5:c.4-193G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001349118.1(SMIM27):​c.-734C>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 0.00336 in 675,518 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (3 hom.)
• Consequence: SMIM27 NM_001349118.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.58
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 9-32551161-C-A is Benign according to our data. Variant chr9-32551161-C-A is described in ClinVar as Benign. ClinVar VariationId is 2659140.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349118.1. 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.4-193G>T		intron	N/A	NP_005793.2
	SMIM27	NM_001349118.1		c.-734C>A		5_prime_UTR	Exon 1 of 3	NP_001336047.1	A0A1B0GUW7
	TOPORS	NM_001195622.2		c.3+1273G>T		intron	N/A	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.4-193G>T		intron	N/A	ENSP00000353735.2	Q9NS56-1
	TOPORS	ENST00000379858.1	TSL:1	c.3+1273G>T		intron	N/A	ENSP00000369187.1	Q9NS56-2
	ENSG00000288684	ENST00000681750.1		c.-239-193G>T		intron	N/A	ENSP00000506413.1	A0A7P0TB70

Frequencies

GnomAD3 genomes AF: 0.00315 AC: 479 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00857

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00473

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.00343 AC: 1794 AN: 523196 Hom.: 3 Cov.: 6 AF XY: 0.00321 AC XY: 889 AN XY: 276814

African (AFR) AF: 0.000749 AC: 11 AN: 14682

American (AMR) AF: 0.00143 AC: 38 AN: 26570

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 19 AN: 15900

East Asian (EAS) AF: 0.00 AC: 0 AN: 31592

South Asian (SAS) AF: 0.000844 AC: 45 AN: 53346

European-Finnish (FIN) AF: 0.00591 AC: 180 AN: 30442

Middle Eastern (MID) AF: 0.000898 AC: 2 AN: 2228

European-Non Finnish (NFE) AF: 0.00445 AC: 1423 AN: 319690

Other (OTH) AF: 0.00264 AC: 76 AN: 28746

GnomAD4 genome AF: 0.00314 AC: 479 AN: 152322 Hom.: 0 Cov.: 32 AF XY: 0.00329 AC XY: 245 AN XY: 74474

African (AFR) AF: 0.000770 AC: 32 AN: 41582

American (AMR) AF: 0.00137 AC: 21 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00857 AC: 91 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00473 AC: 322 AN: 68030

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00445 Hom.: 0

Bravo AF: 0.00241

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.39
DANN	Benign	0.22
PhyloP100		-6.6
PromoterAI		0.0094	Neutral

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: rs549299723; hg19: chr9-32551159;