chr9-32552464-C-G

Position:

chr9-32552464-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 links:

ENSG00000288684 (HGNC:):

ENSG00000288684 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMIM27	NM_001387564.1 linkuse as main transcript	c.30C>G	p.Asp10Glu	missense_variant	1/2	ENST00000692500.1	NP_001374493.1
TOPORS	NM_005802.5 linkuse as main transcript	c.-28G>C		5_prime_UTR_variant	1/3	ENST00000360538.7	NP_005793.2	Q9NS56-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SMIM27	ENST00000692500.1 linkuse as main transcript	c.30C>G	p.Asp10Glu	missense_variant	1/2		NM_001387564.1	ENSP00000508648.1	A0A1B0GUW7
TOPORS	ENST00000360538.7 linkuse as main transcript	c.-28G>C		5_prime_UTR_variant	1/3	1	NM_005802.5	ENSP00000353735.2	Q9NS56-1
ENSG00000288684	ENST00000681750.1 linkuse as main transcript	c.-375G>C		5_prime_UTR_variant	1/20			ENSP00000506413.1	A0A7P0TB70

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

GnomAD3 exomes

AF:

0.0708

AC:

15970

AN:

225640

Hom.:

901

AF XY:

0.0658

AC XY:

8056

AN XY:

122350

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 SAS exome

AF:

0.0293

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

Gnomad4 AFR exome

AF:

0.00958

Gnomad4 AMR exome

AF:

0.168

Gnomad4 ASJ exome

AF:

0.0422

Gnomad4 EAS exome

AF:

0.000153

Gnomad4 SAS exome

AF:

0.0317

Gnomad4 FIN exome

AF:

0.0917

Gnomad4 NFE exome

AF:

0.0685

Gnomad4 OTH exome

AF:

0.0548

GnomAD4 genome

AF:

0.0561

AC:

8554

AN:

152342

Hom.:

393

Cov.:

AF XY:

0.0565

AC XY:

4211

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0130

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.0404

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0217

Gnomad4 FIN

AF:

0.0844

Gnomad4 NFE

AF:

0.0744

Gnomad4 OTH

AF:

0.0374

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.91

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.31

T;T;T;T

MetaRNN

Benign

0.0015

T;T;T;T

GERP RS

-0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.083

gMVP

0.020

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over