rs112583032

Variant names:

• chr5-150297541-G-A
• rs112583032
• NM_001012301.4:c.1383C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-150297541-G-A
• chr5-150297541-G-C
• chr5-150297541-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001012301.4(ARSI):​c.1383C>T​(p.Ala461Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,613,146 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (29 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (23 hom.)
• Consequence: ARSI NM_001012301.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.23
• Publications: 2 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-150297541-G-A is Benign according to our data. Variant chr5-150297541-G-A is described in ClinVar as Benign. ClinVar VariationId is 533758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.22 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0105 (1594/152334) while in subpopulation AFR AF = 0.034 (1412/41572). AF 95% confidence interval is 0.0325. There are 29 homozygotes in GnomAd4. There are 722 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012301.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSI	NM_001012301.4	MANE Select	c.1383C>T	p.Ala461Ala	synonymous	Exon 2 of 2	NP_001012301.1	Q5FYB1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSI	ENST00000328668.8	TSL:1 MANE Select	c.1383C>T	p.Ala461Ala	synonymous	Exon 2 of 2	ENSP00000333395.7	Q5FYB1-1
	ARSI	ENST00000515301.2	TSL:4	c.954C>T	p.Ala318Ala	synonymous	Exon 2 of 2	ENSP00000426879.2	Q5FYB1-2

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1593 AN: 152216 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.00764

GnomAD2 exomes AF: 0.00339 AC: 848 AN: 250276 AF XY: 0.00280

Gnomad AFR exome AF: 0.0350

Gnomad AMR exome AF: 0.00217

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000472

Gnomad NFE exome AF: 0.00162

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00231 AC: 3380 AN: 1460812 Hom.: 23 Cov.: 29 AF XY: 0.00220 AC XY: 1597 AN XY: 726708

African (AFR) AF: 0.0336 AC: 1125 AN: 33476

American (AMR) AF: 0.00239 AC: 107 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26122

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86190

European-Finnish (FIN) AF: 0.000133 AC: 7 AN: 52674

Middle Eastern (MID) AF: 0.00589 AC: 34 AN: 5768

European-Non Finnish (NFE) AF: 0.00169 AC: 1877 AN: 1111818

Other (OTH) AF: 0.00349 AC: 211 AN: 60372

GnomAD4 genome AF: 0.0105 AC: 1594 AN: 152334 Hom.: 29 Cov.: 32 AF XY: 0.00969 AC XY: 722 AN XY: 74496

African (AFR) AF: 0.0340 AC: 1412 AN: 41572

American (AMR) AF: 0.00418 AC: 64 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00147 AC: 100 AN: 68030

Other (OTH) AF: 0.00756 AC: 16 AN: 2116

Alfa AF: 0.00351 Hom.: 6

Bravo AF: 0.0113

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.00180

EpiControl AF: 0.00196

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.24
DANN	Benign	0.65
PhyloP100		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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: rs112583032; hg19: chr5-149677104; COSMIC: COSV60817052; COSMIC: COSV60817052;