9-32552464-C-T

Variant names:

• chr9-32552464-C-T
• rs15014
• NM_001387564.1:c.30C>T
• SMIM27 p.Asp10Asp

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001387564.1(SMIM27):​c.30C>T​(p.Asp10Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,448,222 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: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SMIM27 NM_001387564.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730
• Publications: 0 publications found

Genes affected

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

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]

TOPORS Gene-Disease associations (from GenCC):

• retinitis pigmentosa 31

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• TOPORS-related retinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ciliopathy

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ENSG00000288684 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=0.73 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387564.1. 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
	SMIM27	NM_001387564.1	MANE Select	c.30C>T	p.Asp10Asp	synonymous	Exon 1 of 2	NP_001374493.1	A0A1B0GUW7
	TOPORS	NM_005802.5	MANE Select	c.-28G>A		5_prime_UTR	Exon 1 of 3	NP_005793.2
	SMIM27	NM_001349118.1		c.30C>T	p.Asp10Asp	synonymous	Exon 2 of 3	NP_001336047.1	A0A1B0GUW7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM27	ENST00000692500.1	MANE Select	c.30C>T	p.Asp10Asp	synonymous	Exon 1 of 2	ENSP00000508648.1	A0A1B0GUW7
	TOPORS	ENST00000360538.7	TSL:1 MANE Select	c.-28G>A		5_prime_UTR	Exon 1 of 3	ENSP00000353735.2	Q9NS56-1
	TOPORS	ENST00000379858.1	TSL:1	c.-28G>A		5_prime_UTR	Exon 1 of 2	ENSP00000369187.1	Q9NS56-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000621 AC: 9 AN: 1448222 Hom.: 0 Cov.: 32 AF XY: 0.00000695 AC XY: 5 AN XY: 719124

African (AFR) AF: 0.00 AC: 0 AN: 33306

American (AMR) AF: 0.00 AC: 0 AN: 42688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25900

East Asian (EAS) AF: 0.00 AC: 0 AN: 39298

South Asian (SAS) AF: 0.00 AC: 0 AN: 84174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5084

European-Non Finnish (NFE) AF: 0.00000814 AC: 9 AN: 1106056

Other (OTH) AF: 0.00 AC: 0 AN: 59806

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		0.73
PromoterAI		0.024	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs15014; hg19: chr9-32552462;