rs12522210

Variant names:

• chr5-150300081-T-G
• rs12522210
• NM_001012301.4:c.312-1469A>C

Variant summary

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

The NM_001012301.4(ARSI):​c.312-1469A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,132 control chromosomes in the GnomAD database, including 58,901 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 0.88 (58901 hom., cov: 31)
• Consequence: ARSI NM_001012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• Publications: 1 publications found

Genes affected

ARSI (HGNC:32521): (arylsulfatase family member I) This gene encodes a protein that belongs to a large family of sulfatases that hydrolyze sulfate esters and sulfamates. Members of this family play a role in several cellular processes, including hormone synthesis, cell signaling in development and degradation of macromolecules. The protein encoded by this gene is thought to be secreted, and to function in extracellular space. [provided by RefSeq, Jul 2016]

ARSI Gene-Disease associations (from GenCC):

• autosomal recessive spastic paraplegia type 66

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSI	NM_001012301.4	c.312-1469A>C		intron_variant	Intron 1 of 1	ENST00000328668.8	NP_001012301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSI	ENST00000328668.8	c.312-1469A>C		intron_variant	Intron 1 of 1	1	NM_001012301.4	ENSP00000333395.7
ARSI	ENST00000515301.2	c.-118-1469A>C		intron_variant	Intron 1 of 1	4		ENSP00000426879.2
ARSI	ENST00000509146.1	c.-118-1469A>C		intron_variant	Intron 1 of 1	4		ENSP00000420955.1

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133435 AN: 152014 Hom.: 58860 Cov.: 31

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.957

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.868

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

GnomAD4 genome AF: 0.878 AC: 133528 AN: 152132 Hom.: 58901 Cov.: 31 AF XY: 0.877 AC XY: 65209 AN XY: 74386

African (AFR) AF: 0.805 AC: 33377 AN: 41468

American (AMR) AF: 0.790 AC: 12072 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3081 AN: 3472

East Asian (EAS) AF: 0.867 AC: 4487 AN: 5174

South Asian (SAS) AF: 0.881 AC: 4243 AN: 4814

European-Finnish (FIN) AF: 0.957 AC: 10134 AN: 10592

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.929 AC: 63183 AN: 68022

Other (OTH) AF: 0.868 AC: 1836 AN: 2114

Alfa AF: 0.888 Hom.: 18464

Bravo AF: 0.860

Asia WGS AF: 0.874 AC: 3038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.51
PhyloP100		-0.11
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: rs12522210; hg19: chr5-149679644;