5-150302647-A-G

Variant names:

• chr5-150302647-A-G
• rs968431
• NM_001012301.4:c.-274T>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.-274T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 328,504 control chromosomes in the GnomAD database, including 85,526 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 0.71 (38435 hom., cov: 34)
  • Exomes 𝑓: 0.73 (47091 hom.)
• Consequence: ARSI NM_001012301.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416
• Publications: 4 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=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.739 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSI	NM_001012301.4	MANE Select	c.-274T>C		5_prime_UTR	Exon 1 of 2	NP_001012301.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSI	ENST00000328668.8	TSL:1 MANE Select	c.-274T>C		5_prime_UTR	Exon 1 of 2	ENSP00000333395.7
	ARSI	ENST00000515301.2	TSL:4	c.-118-4035T>C		intron	N/A	ENSP00000426879.2
	ARSI	ENST00000509146.1	TSL:4	c.-118-4035T>C		intron	N/A	ENSP00000420955.1

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107955 AN: 152018 Hom.: 38414 Cov.: 34

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.695

GnomAD4 exome AF: 0.729 AC: 128539 AN: 176372 Hom.: 47091 Cov.: 2 AF XY: 0.729 AC XY: 65214 AN XY: 89494

African (AFR) AF: 0.675 AC: 3457 AN: 5118

American (AMR) AF: 0.619 AC: 3109 AN: 5020

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 4615 AN: 6476

East Asian (EAS) AF: 0.709 AC: 11373 AN: 16042

South Asian (SAS) AF: 0.730 AC: 1265 AN: 1734

European-Finnish (FIN) AF: 0.741 AC: 11510 AN: 15540

Middle Eastern (MID) AF: 0.652 AC: 627 AN: 962

European-Non Finnish (NFE) AF: 0.740 AC: 84238 AN: 113824

Other (OTH) AF: 0.716 AC: 8345 AN: 11656

GnomAD4 genome AF: 0.710 AC: 108020 AN: 152132 Hom.: 38435 Cov.: 34 AF XY: 0.708 AC XY: 52629 AN XY: 74378

African (AFR) AF: 0.670 AC: 27841 AN: 41526

American (AMR) AF: 0.649 AC: 9921 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2467 AN: 3470

East Asian (EAS) AF: 0.669 AC: 3439 AN: 5142

South Asian (SAS) AF: 0.733 AC: 3536 AN: 4824

European-Finnish (FIN) AF: 0.739 AC: 7833 AN: 10604

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50610 AN: 67958

Other (OTH) AF: 0.695 AC: 1466 AN: 2108

Alfa AF: 0.736 Hom.: 21058

Bravo AF: 0.698

Asia WGS AF: 0.712 AC: 2475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.7
DANN	Benign	0.78
PhyloP100		-0.42
PromoterAI		0.012	Neutral
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: rs968431; hg19: chr5-149682210;