NM_001387564.1:c.45+129C>T

Variant names:

• chr9-32552608-C-T
• rs187268836
• NM_001387564.1:c.45+129C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001387564.1(SMIM27):​c.45+129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 796,116 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (5 hom.)
• Consequence: SMIM27 NM_001387564.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.420
• 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, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BS2: High Homozygotes in GnomAdExome4 at 5 gene

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.45+129C>T		intron	N/A	NP_001374493.1	A0A1B0GUW7
	SMIM27	NM_001349118.1		c.45+129C>T		intron	N/A	NP_001336047.1	A0A1B0GUW7
	SMIM27	NM_001349119.2		c.45+129C>T		intron	N/A	NP_001336048.1	A0A1B0GUW7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM27	ENST00000692500.1	MANE Select	c.45+129C>T		intron	N/A	ENSP00000508648.1	A0A1B0GUW7
	SMIM27	ENST00000644531.2		c.174C>T	p.Leu58Leu	synonymous	Exon 1 of 1	ENSP00000521002.1	A0A2R8Y3B0
	SMIM27	ENST00000635960.1	TSL:5	c.66C>T	p.Leu22Leu	synonymous	Exon 1 of 2	ENSP00000492552.1	A0A1W2PRY6

Frequencies

GnomAD3 genomes AF: 0.00178 AC: 271 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0170

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00164 AC: 1055 AN: 643818 Hom.: 5 Cov.: 8 AF XY: 0.00161 AC XY: 550 AN XY: 340834

African (AFR) AF: 0.00 AC: 0 AN: 17336

American (AMR) AF: 0.000643 AC: 22 AN: 34200

Ashkenazi Jewish (ASJ) AF: 0.00434 AC: 87 AN: 20040

East Asian (EAS) AF: 0.00 AC: 0 AN: 32330

South Asian (SAS) AF: 0.00 AC: 0 AN: 63756

European-Finnish (FIN) AF: 0.0142 AC: 591 AN: 41622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2610

European-Non Finnish (NFE) AF: 0.000760 AC: 303 AN: 398816

Other (OTH) AF: 0.00157 AC: 52 AN: 33108

GnomAD4 genome AF: 0.00178 AC: 271 AN: 152298 Hom.: 0 Cov.: 33 AF XY: 0.00250 AC XY: 186 AN XY: 74456

African (AFR) AF: 0.0000241 AC: 1 AN: 41566

American (AMR) AF: 0.00105 AC: 16 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.0170 AC: 180 AN: 10604

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

European-Non Finnish (NFE) AF: 0.000941 AC: 64 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000530 Hom.: 0

Bravo AF: 0.000597

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Retinitis Pigmentosa, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.96
PhyloP100		-0.42
PromoterAI		-0.073	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs187268836; hg19: chr9-32552606;