9-32552464-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001387564.1(SMIM27):c.30C>G(p.Asp10Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0648 in 1,600,362 control chromosomes in the GnomAD database, including 4,150 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 393 hom., cov: 33)

Exomes 𝑓: 0.066 ( 3757 hom. )

Consequence

SMIM27
NM_001387564.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.730

Publications

8 publications found

Variant links:

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]

SMIM27 links:

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

TOPORS links:

ENSG00000288684 (HGNC:):

ENSG00000288684 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015094578).

BP6

Variant 9-32552464-C-G is Benign according to our data. Variant chr9-32552464-C-G is described in ClinVar as Benign. ClinVar VariationId is 366574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMIM27	NM_001387564.1	MANE Select	c.30C>G	p.Asp10Glu	missense	Exon 1 of 2	NP_001374493.1	A0A1B0GUW7
TOPORS	NM_005802.5	MANE Select	c.-28G>C		5_prime_UTR	Exon 1 of 3	NP_005793.2
SMIM27	NM_001349118.1		c.30C>G	p.Asp10Glu	missense	Exon 2 of 3	NP_001336047.1	A0A1B0GUW7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMIM27	ENST00000692500.1	MANE Select	c.30C>G	p.Asp10Glu	missense	Exon 1 of 2	ENSP00000508648.1	A0A1B0GUW7
TOPORS	ENST00000360538.7	TSL:1 MANE Select	c.-28G>C		5_prime_UTR	Exon 1 of 3	ENSP00000353735.2	Q9NS56-1
TOPORS	ENST00000379858.1	TSL:1	c.-28G>C		5_prime_UTR	Exon 1 of 2	ENSP00000369187.1	Q9NS56-2

Frequencies

GnomAD3 genomes

AF:

0.0561

AC:

8545

AN:

152224

Hom.:

394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.0912

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.0404

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0213

Gnomad FIN

AF:

0.0844

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0743

Gnomad OTH

AF:

0.0378

GnomAD2 exomes

AF:

0.0708

AC:

15970

AN:

225640

AF XY:

0.0658

show subpopulations

Gnomad AFR exome

AF:

0.0100

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.0413

Gnomad EAS exome

AF:

0.000176

Gnomad FIN exome

AF:

0.0866

Gnomad NFE exome

AF:

0.0691

Gnomad OTH exome

AF:

0.0637

GnomAD4 exome

AF:

0.0657

AC:

95141

AN:

1448020

Hom.:

3757

Cov.:

AF XY:

0.0646

AC XY:

46430

AN XY:

719032

show subpopulations

African (AFR)

AF:

0.00958

AC:

319

AN:

33304

American (AMR)

AF:

0.168

AC:

7161

AN:

42642

Ashkenazi Jewish (ASJ)

AF:

0.0422

AC:

1094

AN:

25900

East Asian (EAS)

AF:

0.000153

AC:

AN:

39298

South Asian (SAS)

AF:

0.0317

AC:

2665

AN:

84168

European-Finnish (FIN)

AF:

0.0917

AC:

4761

AN:

51898

Middle Eastern (MID)

AF:

0.0177

AC:

AN:

5084

European-Non Finnish (NFE)

AF:

0.0685

AC:

75767

AN:

1105920

Other (OTH)

AF:

0.0548

AC:

3278

AN:

59806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

4539

9078

13618

18157

22696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2724

5448

8172

10896

13620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0561

AC:

8554

AN:

152342

Hom.:

393

Cov.:

AF XY:

0.0565

AC XY:

4211

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0130

AC:

542

AN:

41586

American (AMR)

AF:

0.108

AC:

1645

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0404

AC:

140

AN:

3468

East Asian (EAS)

AF:

0.000578

AC:

AN:

5190

South Asian (SAS)

AF:

0.0217

AC:

105

AN:

4828

European-Finnish (FIN)

AF:

0.0844

AC:

897

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0744

AC:

5058

AN:

68026

Other (OTH)

AF:

0.0374

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

419

839

1258

1678

2097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0668

Hom.:

Bravo

AF:

0.0557

TwinsUK

AF:

0.0647

AC:

240

ALSPAC

AF:

0.0656

AC:

253

ESP6500AA

AF:

0.0114

AC:

ESP6500EA

AF:

0.0710

AC:

611

ExAC

AF:

0.0599

AC:

7253

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.91

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0015

PhyloP100

0.73

GERP RS

-0.20

PromoterAI

-0.00060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.083

gMVP

0.020

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over