9-34637693-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005866.4(SIGMAR1):c.5A>C(p.Gln2Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,526,870 control chromosomes in the GnomAD database, including 24,420 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q2Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.18 ( 2474 hom., cov: 33)

Exomes 𝑓: 0.17 ( 21946 hom. )

Consequence

SIGMAR1
NM_005866.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.168

Variant links:

Genes affected

SIGMAR1 (HGNC:8157): (sigma non-opioid intracellular receptor 1) This gene encodes a receptor protein that interacts with a variety of psychotomimetic drugs, including cocaine and amphetamines. The receptor is believed to play an important role in the cellular functions of various tissues associated with the endocrine, immune, and nervous systems. As indicated by its previous name, opioid receptor sigma 1 (OPRS1), the product of this gene was erroneously thought to function as an opioid receptor; it is now thought to be a non-opioid receptor. Mutations in this gene has been associated with juvenile amyotrophic lateral sclerosis 16. Alternative splicing of this gene results in transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2013]

SIGMAR1 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=0.0011137724).

BP6

Variant 9-34637693-T-G is Benign according to our data. Variant chr9-34637693-T-G is described in ClinVar as [Benign]. Clinvar id is 586584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-34637693-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGMAR1	NM_005866.4 link	c.5A>C	p.Gln2Pro	missense_variant	Exon 1 of 4	ENST00000277010.9	NP_005857.1	Q99720-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGMAR1	ENST00000277010.9 link	c.5A>C	p.Gln2Pro	missense_variant	Exon 1 of 4	1	NM_005866.4	ENSP00000277010.4		Q99720-1

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27181

AN:

152154

Hom.:

2475

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.186

GnomAD3 exomes

AF:

0.201

AC:

25339

AN:

125854

Hom.:

2830

AF XY:

0.197

AC XY:

13584

AN XY:

68932

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.278

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.315

Gnomad SAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.175

AC:

240232

AN:

1374600

Hom.:

21946

Cov.:

AF XY:

0.175

AC XY:

118299

AN XY:

677516

show subpopulations

Gnomad4 AFR exome

AF:

0.181

Gnomad4 AMR exome

AF:

0.268

Gnomad4 ASJ exome

AF:

0.139

Gnomad4 EAS exome

AF:

0.313

Gnomad4 SAS exome

AF:

0.192

Gnomad4 FIN exome

AF:

0.131

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.173

GnomAD4 genome

AF:

0.178

AC:

27180

AN:

152270

Hom.:

2474

Cov.:

AF XY:

0.179

AC XY:

13308

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.184

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.313

Gnomad4 SAS

AF:

0.192

Gnomad4 FIN

AF:

0.133

Gnomad4 NFE

AF:

0.162

Gnomad4 OTH

AF:

0.184

Alfa

AF:

0.161

Hom.:

403

Bravo

AF:

0.188

TwinsUK

AF:

0.162

AC:

601

ALSPAC

AF:

0.173

AC:

667

ESP6500AA

AF:

0.134

AC:

472

ESP6500EA

AF:

0.116

AC:

752

ExAC

AF:

0.0809

AC:

3361

Asia WGS

AF:

0.256

AC:

890

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Nov 17, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31159747, 30917570, 21549171, 22818711, 9857962, 22561649) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Autosomal recessive distal spinal muscular atrophy 2

Benign:1

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive distal spinal muscular atrophy 2;C3280587:Amyotrophic lateral sclerosis type 16

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.091

T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.75

T;T

MetaRNN

Benign

0.0011

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.55

N;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.030

N;N

REVEL

Benign

0.14

Sift

Benign

0.34

T;T

Sift4G

Benign

0.43

T;T

Polyphen

0.0

B;.

Vest4

0.11

MPC

0.96

ClinPred

0.00034

GERP RS

0.91

Varity_R

0.42

gMVP

0.54

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