NM_001012301.4:c.312-1088A>G

Variant names:

• chr5-150299700-T-C
• rs9324643
• NM_001012301.4:c.312-1088A>G

Variant summary

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

The NM_001012301.4(ARSI):​c.312-1088A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 151,782 control chromosomes in the GnomAD database, including 48,771 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 0.80 (48771 hom., cov: 29)
• Consequence: ARSI NM_001012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSI	NM_001012301.4	c.312-1088A>G		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.312-1088A>G		intron_variant	Intron 1 of 1	1	NM_001012301.4	ENSP00000333395.7
ARSI	ENST00000515301.2	c.-118-1088A>G		intron_variant	Intron 1 of 1	4		ENSP00000426879.2
ARSI	ENST00000509146.1	c.-118-1088A>G		intron_variant	Intron 1 of 1	4		ENSP00000420955.1

Frequencies

GnomAD3 genomes AF: 0.796 AC: 120686 AN: 151664 Hom.: 48766 Cov.: 29

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.788

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

GnomAD4 genome AF: 0.795 AC: 120727 AN: 151782 Hom.: 48771 Cov.: 29 AF XY: 0.793 AC XY: 58826 AN XY: 74158

African (AFR) AF: 0.646 AC: 26716 AN: 41340

American (AMR) AF: 0.726 AC: 11075 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2812 AN: 3472

East Asian (EAS) AF: 0.848 AC: 4373 AN: 5158

South Asian (SAS) AF: 0.817 AC: 3888 AN: 4760

European-Finnish (FIN) AF: 0.881 AC: 9276 AN: 10534

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.881 AC: 59887 AN: 67958

Other (OTH) AF: 0.790 AC: 1664 AN: 2106

Alfa AF: 0.842 Hom.: 78540

Bravo AF: 0.775

Asia WGS AF: 0.821 AC: 2853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.75
PhyloP100		-1.2
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: rs9324643; hg19: chr5-149679263;