Variant 9-34635601-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:4

Conservation

PhyloP100: 0.436

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:

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ACMG classification

Classification made for transcript

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/exons	MANE	UniProt
SIGMAR1	NM_005866.4 linkuse as main transcript	c.*31A>G		3_prime_UTR_variant	4/4	ENST00000277010.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGMAR1	ENST00000277010.9 linkuse as main transcript	c.*31A>G		3_prime_UTR_variant	4/4	1	NM_005866.4	P1	Q99720-1

Frequencies

GnomAD3 genomes

AF:

0.988

AC:

150443

AN:

152250

Hom.:

74351

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.998

AC XY:

725359

AN XY:

726978

show subpopulations

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.:

AF XY:

0.988

AC XY:

73622

AN XY:

74498

show subpopulations

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:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Amyotrophic lateral sclerosis type 16

Uncertain:1Benign:1

Uncertain significance, no assertion criteria provided	literature only	OMIM	Jul 24, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

Autosomal recessive distal spinal muscular atrophy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

This variant is associated with the following publications: (PMID: 26205306) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

Cadd

Benign

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

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