5-150298123-C-T

Variant names:

• chr5-150298123-C-T
• rs114744538
• NM_001012301.4:c.801G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001012301.4(ARSI):​c.801G>A​(p.Val267Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,613,776 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (100 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (66 hom.)
• Consequence: ARSI NM_001012301.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.554
• 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 5-150298123-C-T is Benign according to our data. Variant chr5-150298123-C-T is described in ClinVar as Benign. ClinVar VariationId is 533755.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.554 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0615 is higher than 0.05.

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.801G>A	p.Val267Val	synonymous	Exon 2 of 2	NP_001012301.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSI	ENST00000328668.8	TSL:1 MANE Select	c.801G>A	p.Val267Val	synonymous	Exon 2 of 2	ENSP00000333395.7
	ARSI	ENST00000515301.2	TSL:4	c.372G>A	p.Val124Val	synonymous	Exon 2 of 2	ENSP00000426879.2
	ARSI	ENST00000509146.1	TSL:4	c.*112G>A		downstream_gene	N/A	ENSP00000420955.1

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 2808 AN: 152104 Hom.: 100 Cov.: 32

Gnomad AFR AF: 0.0635

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00753

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00510 AC: 1278 AN: 250700 AF XY: 0.00348

Gnomad AFR exome AF: 0.0672

Gnomad AMR exome AF: 0.00365

Gnomad ASJ exome AF: 0.00229

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00201 AC: 2937 AN: 1461554 Hom.: 66 Cov.: 30 AF XY: 0.00172 AC XY: 1249 AN XY: 727084

African (AFR) AF: 0.0662 AC: 2218 AN: 33480

American (AMR) AF: 0.00429 AC: 192 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00195 AC: 51 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86254

European-Finnish (FIN) AF: 0.0000377 AC: 2 AN: 53116

Middle Eastern (MID) AF: 0.00451 AC: 26 AN: 5768

European-Non Finnish (NFE) AF: 0.000159 AC: 177 AN: 1111992

Other (OTH) AF: 0.00435 AC: 263 AN: 60392

GnomAD4 genome AF: 0.0185 AC: 2816 AN: 152222 Hom.: 100 Cov.: 32 AF XY: 0.0181 AC XY: 1345 AN XY: 74416

African (AFR) AF: 0.0636 AC: 2639 AN: 41524

American (AMR) AF: 0.00752 AC: 115 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68002

Other (OTH) AF: 0.0156 AC: 33 AN: 2114

Alfa AF: 0.00915 Hom.: 30

Bravo AF: 0.0212

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

ClinVar submissions as Germline

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	-0.49
CADD	Benign	5.0
DANN	Benign	0.66
PhyloP100		-0.55
Mutation Taster		=93/7	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: rs114744538; hg19: chr5-149677686;