rs9510730

Variant names:

• chr13-23420124-G-A
• rs9510730
• NM_014363.6:c.-501-8384C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-23420124-G-A
• chr13-23420124-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014363.6(SACS):​c.-501-8384C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,072 control chromosomes in the GnomAD database, including 46,675 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (46675 hom., cov: 32)
• Consequence: SACS NM_014363.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 7 publications found

Genes affected

SACS (HGNC:10519): (sacsin molecular chaperone) This gene encodes the sacsin protein, which includes a UbL domain at the N-terminus, a DnaJ domain, and a HEPN domain at the C-terminus. The gene is highly expressed in the central nervous system, also found in skin, skeletal muscles and at low levels in the pancreas. This gene includes a very large exon spanning more than 12.8 kb. Mutations in this gene result in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disorder characterized by early-onset cerebellar ataxia with spasticity and peripheral neuropathy. The authors of a publication on the effects of siRNA-mediated sacsin knockdown concluded that sacsin protects against mutant ataxin-1 and suggest that "the large multi-domain sacsin protein is able to recruit Hsp70 chaperone action and has the potential to regulate the effects of other ataxia proteins" (Parfitt et al., PubMed: 19208651). A pseudogene associated with this gene is located on chromosome 11. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

SACS-AS1 (HGNC:39835): (SACS antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SACS	NM_014363.6	c.-501-8384C>T		intron_variant	Intron 1 of 9	ENST00000382292.9	NP_055178.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SACS	ENST00000382292.9	c.-501-8384C>T		intron_variant	Intron 1 of 9	5	NM_014363.6	ENSP00000371729.3

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118638 AN: 151954 Hom.: 46630 Cov.: 32

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.850

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.781

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.781 AC: 118741 AN: 152072 Hom.: 46675 Cov.: 32 AF XY: 0.782 AC XY: 58174 AN XY: 74344

African (AFR) AF: 0.719 AC: 29805 AN: 41464

American (AMR) AF: 0.675 AC: 10310 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2699 AN: 3466

East Asian (EAS) AF: 0.831 AC: 4286 AN: 5160

South Asian (SAS) AF: 0.916 AC: 4412 AN: 4818

European-Finnish (FIN) AF: 0.826 AC: 8752 AN: 10596

Middle Eastern (MID) AF: 0.849 AC: 248 AN: 292

European-Non Finnish (NFE) AF: 0.821 AC: 55798 AN: 67984

Other (OTH) AF: 0.782 AC: 1651 AN: 2112

Alfa AF: 0.802 Hom.: 91697

Bravo AF: 0.759

Asia WGS AF: 0.845 AC: 2938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.57
DANN	Benign	0.50
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9510730; hg19: chr13-23994263;