NM_001012301.4:c.311+1034C>T

Variant names:

• chr5-150301029-G-A
• rs930210
• NM_001012301.4:c.311+1034C>T

Variant summary

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

The NM_001012301.4(ARSI):​c.311+1034C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,072 control chromosomes in the GnomAD database, including 1,263 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 0.11 (1263 hom., cov: 32)
• Consequence: ARSI NM_001012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSI	NM_001012301.4	c.311+1034C>T		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.311+1034C>T		intron_variant	Intron 1 of 1	1	NM_001012301.4	ENSP00000333395.7
ARSI	ENST00000515301.2	c.-118-2417C>T		intron_variant	Intron 1 of 1	4		ENSP00000426879.2
ARSI	ENST00000509146.1	c.-118-2417C>T		intron_variant	Intron 1 of 1	4		ENSP00000420955.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15998 AN: 151954 Hom.: 1252 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0540

Gnomad AMR AF: 0.0742

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0821

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0493

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.106 AC: 16045 AN: 152072 Hom.: 1263 Cov.: 32 AF XY: 0.106 AC XY: 7892 AN XY: 74332

African (AFR) AF: 0.219 AC: 9055 AN: 41436

American (AMR) AF: 0.0741 AC: 1133 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 277 AN: 3470

East Asian (EAS) AF: 0.140 AC: 724 AN: 5166

South Asian (SAS) AF: 0.0822 AC: 396 AN: 4818

European-Finnish (FIN) AF: 0.0762 AC: 807 AN: 10586

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0493 AC: 3354 AN: 67986

Other (OTH) AF: 0.102 AC: 216 AN: 2114

Alfa AF: 0.0580 Hom.: 176

Bravo AF: 0.111

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.88
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: rs930210; hg19: chr5-149680592; COSMIC: COSV60817023;