chr5-150298288-A-G

Variant names:

• chr5-150298288-A-G
• rs6579784
• NM_001012301.4:c.636T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001012301.4(ARSI):​c.636T>C​(p.Tyr212Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,613,410 control chromosomes in the GnomAD database, including 796,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 1.0 (75565 hom., cov: 33)
  • Exomes 𝑓: 0.99 (721406 hom.)
• Consequence: ARSI NM_001012301.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.12
• Publications: 13 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 5-150298288-A-G is Benign according to our data. Variant chr5-150298288-A-G is described in ClinVar as Benign. ClinVar VariationId is 1168278.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 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.636T>C	p.Tyr212Tyr	synonymous	Exon 2 of 2	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.636T>C	p.Tyr212Tyr	synonymous	Exon 2 of 2	ENSP00000333395.7	Q5FYB1-1
	ARSI	ENST00000515301.2	TSL:4	c.207T>C	p.Tyr69Tyr	synonymous	Exon 2 of 2	ENSP00000426879.2	Q5FYB1-2
	ARSI	ENST00000509146.1	TSL:4	c.207T>C	p.Tyr69Tyr	synonymous	Exon 2 of 2	ENSP00000420955.1	D6RDH0

Frequencies

GnomAD3 genomes AF: 0.996 AC: 151585 AN: 152166 Hom.: 75506 Cov.: 33

Gnomad AFR AF: 0.998

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.998

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.996

GnomAD2 exomes AF: 0.996 AC: 246589 AN: 247480 AF XY: 0.996

Gnomad AFR exome AF: 0.999

Gnomad AMR exome AF: 0.998

Gnomad ASJ exome AF: 0.996

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.994

Gnomad OTH exome AF: 0.995

GnomAD4 exome AF: 0.994 AC: 1451934 AN: 1461126 Hom.: 721406 Cov.: 93 AF XY: 0.994 AC XY: 722354 AN XY: 726834

African (AFR) AF: 0.999 AC: 33437 AN: 33474

American (AMR) AF: 0.998 AC: 44601 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 26030 AN: 26118

East Asian (EAS) AF: 1.00 AC: 39680 AN: 39680

South Asian (SAS) AF: 0.999 AC: 86120 AN: 86220

European-Finnish (FIN) AF: 0.999 AC: 52965 AN: 53002

Middle Eastern (MID) AF: 0.995 AC: 5740 AN: 5766

European-Non Finnish (NFE) AF: 0.992 AC: 1103328 AN: 1111846

Other (OTH) AF: 0.995 AC: 60033 AN: 60348

GnomAD4 genome AF: 0.996 AC: 151703 AN: 152284 Hom.: 75565 Cov.: 33 AF XY: 0.997 AC XY: 74211 AN XY: 74448

African (AFR) AF: 0.998 AC: 41489 AN: 41552

American (AMR) AF: 0.998 AC: 15268 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3460 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5173 AN: 5174

South Asian (SAS) AF: 0.998 AC: 4809 AN: 4818

European-Finnish (FIN) AF: 1.00 AC: 10621 AN: 10626

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.993 AC: 67574 AN: 68018

Other (OTH) AF: 0.996 AC: 2104 AN: 2112

Alfa AF: 0.994 Hom.: 45327

Bravo AF: 0.996

Asia WGS AF: 0.999 AC: 3474 AN: 3478

EpiCase AF: 0.993

EpiControl AF: 0.994

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.027
DANN	Benign	0.39
PhyloP100		-1.1
Mutation Taster		=90/10	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: rs6579784; hg19: chr5-149677851; COSMIC: COSV108121714;