rs968431

Variant names:

• chr5-150302647-A-C
• rs968431
• NM_001012301.4:c.-274T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-150302647-A-C
• chr5-150302647-A-G
• chr5-150302647-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001012301.4(ARSI):​c.-274T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000566 in 176,802 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000057 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSI	NM_001012301.4	c.-274T>G		5_prime_UTR_variant	Exon 1 of 2	ENST00000328668.8	NP_001012301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSI	ENST00000328668.8	c.-274T>G		5_prime_UTR_variant	Exon 1 of 2	1	NM_001012301.4	ENSP00000333395.7
ARSI	ENST00000515301.2	c.-118-4035T>G		intron_variant	Intron 1 of 1	4		ENSP00000426879.2
ARSI	ENST00000509146.1	c.-118-4035T>G		intron_variant	Intron 1 of 1	4		ENSP00000420955.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000566 AC: 1 AN: 176802 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 89696

African (AFR) AF: 0.00 AC: 0 AN: 5136

American (AMR) AF: 0.00 AC: 0 AN: 5034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6496

East Asian (EAS) AF: 0.0000622 AC: 1 AN: 16080

South Asian (SAS) AF: 0.00 AC: 0 AN: 1740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 962

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 114102

Other (OTH) AF: 0.00 AC: 0 AN: 11680

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.5
DANN	Benign	0.81
PhyloP100		-0.42
PromoterAI		-0.0032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;