9-32551161-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001349118.1(SMIM27):​c.-734C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000191 in 523,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: SMIM27 NM_001349118.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000191 AC: 1 AN: 523206 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 276818

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 14684

American (AMR) AF: 0.00 AC: 0 AN: 26570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15900

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 53346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2228

European-Non Finnish (NFE) AF: 0.00000313 AC: 1 AN: 319698

Other (OTH) AF: 0.00 AC: 0 AN: 28746

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.47
DANN	Benign	0.44
PhyloP100		-6.6
PromoterAI		0.042	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;