NM_005866.4:c.*31A>G

Variant names:

• chr9-34635601-T-C
• rs4879809
• NM_005866.4:c.*31A>G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_005866.4(SIGMAR1):​c.*31A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,613,774 control chromosomes in the GnomAD database, including 802,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (74404 hom., cov: 36)
  • Exomes 𝑓: 1.0 (727730 hom.)
• Consequence: SIGMAR1 NM_005866.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:5
• Conservation: PhyloP100: 0.436

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 9-34635601-T-C is Benign according to our data. Variant chr9-34635601-T-C is described in ClinVar as [Benign]. Clinvar id is 208122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGMAR1	NM_005866.4	c.*31A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000277010.9	NP_005857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGMAR1	ENST00000277010	c.*31A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_005866.4	ENSP00000277010.4

Frequencies

GnomAD3 genomes AF: 0.988 AC: 150443 AN: 152250 Hom.: 74351 Cov.: 36

Gnomad AFR AF: 0.961

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.995

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.989

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.991

GnomAD3 exomes AF: 0.996 AC: 248455 AN: 249560 Hom.: 123691 AF XY: 0.996 AC XY: 134514 AN XY: 135078

Gnomad AFR exome AF: 0.960

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 0.998

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.991

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.996

GnomAD4 exome AF: 0.998 AC: 1458373 AN: 1461406 Hom.: 727730 Cov.: 60 AF XY: 0.998 AC XY: 725359 AN XY: 726978

Gnomad4 AFR exome AF: 0.959

Gnomad4 AMR exome AF: 0.997

Gnomad4 ASJ exome AF: 0.998

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.991

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.996

GnomAD4 genome AF: 0.988 AC: 150555 AN: 152368 Hom.: 74404 Cov.: 36 AF XY: 0.988 AC XY: 73622 AN XY: 74498

Gnomad4 AFR AF: 0.961

Gnomad4 AMR AF: 0.995

Gnomad4 ASJ AF: 0.998

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.989

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.991

Alfa AF: 0.997 Hom.: 13642

Bravo AF: 0.986

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Amyotrophic lateral sclerosis type 16 Uncertain:1 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 24, 2015

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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: 26205306) -

Autosomal recessive distal spinal muscular atrophy 2 Benign:1

Jul 15, 2021

Genome-Nilou Lab

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

Jan 20, 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
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs4879809; hg19: chr9-34635598;