chr9-34637693-T-A

Position:

• chr9-34637693-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005866.4(SIGMAR1):​c.5A>T​(p.Gln2Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q2P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SIGMAR1 NM_005866.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1512188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGMAR1	NM_005866.4	c.5A>T	p.Gln2Leu	missense_variant	1/4	ENST00000277010.9	NP_005857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGMAR1	ENST00000277010.9	c.5A>T	p.Gln2Leu	missense_variant	1/4	1	NM_005866.4	ENSP00000277010	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.70	T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.090	N;N
REVEL	Benign	0.10
Sift	Benign	0.14	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.0	B;.
Vest4		0.27
MutPred		0.32		Loss of catalytic residue at Q2 (P = 0.0018);Loss of catalytic residue at Q2 (P = 0.0018);
MVP		0.41
MPC		0.78
ClinPred		0.067	T
GERP RS		0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.49

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

Other links and lift over

dbSNP: rs1800866; hg19: chr9-34637690;