rs79823940

Variant names:

• chr22-50623575-G-A
• rs79823940
• NM_000487.6:c.*1570C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000487.6(ARSA):​c.*1570C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 152,090 control chromosomes in the GnomAD database, including 589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.080 (589 hom., cov: 32)
• Consequence: ARSA NM_000487.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.318
• Publications: 2 publications found

Genes affected

ARSA (HGNC:713): (arylsulfatase A) The protein encoded by this gene hydrolyzes cerebroside sulfate to cerebroside and sulfate. Defects in this gene lead to metachromatic leucodystrophy (MLD), a progressive demyelination disease which results in a variety of neurological symptoms and ultimately death. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2010]

ARSA Gene-Disease associations (from GenCC):

• metachromatic leukodystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health, ClinGen
• metachromatic leukodystrophy, juvenile form

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-50623575-G-A is Benign according to our data. Variant chr22-50623575-G-A is described in ClinVar as Benign. ClinVar VariationId is 342197.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000487.6. 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
	ARSA	NM_000487.6	MANE Select	c.*1570C>T		3_prime_UTR	Exon 8 of 8	NP_000478.3
	ARSA	NM_001085425.3		c.*1570C>T		3_prime_UTR	Exon 9 of 9	NP_001078894.2	A0A0C4DFZ2
	ARSA	NM_001085426.3		c.*1570C>T		3_prime_UTR	Exon 9 of 9	NP_001078895.2	A0A0C4DFZ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSA	ENST00000216124.10	TSL:1 MANE Select	c.*1570C>T		3_prime_UTR	Exon 8 of 8	ENSP00000216124.5	A0A0C4DFZ2
	ARSA	ENST00000608497.1	TSL:3	n.*93+199C>T		intron	N/A	ENSP00000477013.1	V9GYR0
	ARSA	ENST00000610191.1	TSL:6	n.-249C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0799 AC: 12148 AN: 151970 Hom.: 593 Cov.: 32

Gnomad AFR AF: 0.0520

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.0784

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0716

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.0948

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

GnomAD4 genome AF: 0.0799 AC: 12146 AN: 152090 Hom.: 589 Cov.: 32 AF XY: 0.0816 AC XY: 6064 AN XY: 74354

African (AFR) AF: 0.0522 AC: 2168 AN: 41506

American (AMR) AF: 0.0782 AC: 1195 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3472

East Asian (EAS) AF: 0.273 AC: 1403 AN: 5140

South Asian (SAS) AF: 0.142 AC: 682 AN: 4812

European-Finnish (FIN) AF: 0.0716 AC: 759 AN: 10596

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0772 AC: 5247 AN: 67974

Other (OTH) AF: 0.0948 AC: 200 AN: 2110

Alfa AF: 0.0745 Hom.: 62

Bravo AF: 0.0792

Asia WGS AF: 0.196 AC: 681 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Metachromatic leukodystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.73
PhyloP100		0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs79823940; hg19: chr22-51062003;