5-150298762-A-G

Variant names:

• chr5-150298762-A-G
• rs6579786
• NM_001012301.4:c.312-150T>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.312-150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 668,200 control chromosomes in the GnomAD database, including 274,686 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 0.89 (59906 hom., cov: 32)
  • Exomes 𝑓: 0.91 (214780 hom.)
• Consequence: ARSI NM_001012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.923 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.312-150T>C		intron	N/A	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.312-150T>C		intron	N/A	ENSP00000333395.7	Q5FYB1-1
	ARSI	ENST00000515301.2	TSL:4	c.-118-150T>C		intron	N/A	ENSP00000426879.2	Q5FYB1-2
	ARSI	ENST00000509146.1	TSL:4	c.-118-150T>C		intron	N/A	ENSP00000420955.1	D6RDH0

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134657 AN: 152096 Hom.: 59856 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.957

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.874

GnomAD4 exome AF: 0.911 AC: 470130 AN: 515984 Hom.: 214780 AF XY: 0.910 AC XY: 243639 AN XY: 267736

African (AFR) AF: 0.832 AC: 11183 AN: 13448

American (AMR) AF: 0.743 AC: 13796 AN: 18556

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 12489 AN: 14040

East Asian (EAS) AF: 0.871 AC: 27238 AN: 31290

South Asian (SAS) AF: 0.876 AC: 40986 AN: 46770

European-Finnish (FIN) AF: 0.954 AC: 37500 AN: 39288

Middle Eastern (MID) AF: 0.850 AC: 1765 AN: 2076

European-Non Finnish (NFE) AF: 0.930 AC: 299909 AN: 322512

Other (OTH) AF: 0.902 AC: 25264 AN: 28004

GnomAD4 genome AF: 0.885 AC: 134762 AN: 152216 Hom.: 59906 Cov.: 32 AF XY: 0.884 AC XY: 65818 AN XY: 74452

African (AFR) AF: 0.832 AC: 34520 AN: 41490

American (AMR) AF: 0.793 AC: 12128 AN: 15300

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

East Asian (EAS) AF: 0.868 AC: 4493 AN: 5178

South Asian (SAS) AF: 0.882 AC: 4251 AN: 4822

European-Finnish (FIN) AF: 0.957 AC: 10159 AN: 10616

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

European-Non Finnish (NFE) AF: 0.929 AC: 63162 AN: 68016

Other (OTH) AF: 0.875 AC: 1852 AN: 2116

Alfa AF: 0.898 Hom.: 7661

Bravo AF: 0.868

Asia WGS AF: 0.877 AC: 3049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.66
PhyloP100		0.13
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: rs6579786; hg19: chr5-149678325;