17-68348275-T-C

Variant names:

• chr17-68348275-T-C
• rs1558875
• NM_001267727.2:c.454+1103T>C

Variant summary

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

The NM_001267727.2(ARSG):​c.454+1103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,968 control chromosomes in the GnomAD database, including 17,641 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 0.48 (17641 hom., cov: 31)
• Consequence: ARSG NM_001267727.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• Publications: 5 publications found

Genes affected

ARSG (HGNC:24102): (arylsulfatase G) The protein encoded by this gene belongs to the sulfatase enzyme family. Sulfatases hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules. This protein displays arylsulfatase activity at acidic pH, as is typical of lysosomal sulfatases, and has been shown to localize in the lysosomes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

ARSG Gene-Disease associations (from GenCC):

• Usher syndrome, type 4

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• Usher syndrome type 3

  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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001267727.2. 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
	ARSG	NM_001267727.2	MANE Select	c.454+1103T>C		intron	N/A	NP_001254656.1	Q96EG1
	ARSG	NM_001352899.2		c.454+1103T>C		intron	N/A	NP_001339828.1	Q96EG1
	ARSG	NM_001352900.2		c.454+1103T>C		intron	N/A	NP_001339829.1	Q96EG1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSG	ENST00000621439.5	TSL:5 MANE Select	c.454+1103T>C		intron	N/A	ENSP00000480910.1	Q96EG1
	ARSG	ENST00000448504.6	TSL:1	c.454+1103T>C		intron	N/A	ENSP00000407193.2	Q96EG1
	ARSG	ENST00000452479.6	TSL:5	c.-39+1103T>C		intron	N/A	ENSP00000413953.2	J9JIG6

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72258 AN: 151850 Hom.: 17638 Cov.: 31

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.476 AC: 72286 AN: 151968 Hom.: 17641 Cov.: 31 AF XY: 0.472 AC XY: 35055 AN XY: 74272

African (AFR) AF: 0.371 AC: 15351 AN: 41424

American (AMR) AF: 0.560 AC: 8544 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1815 AN: 3472

East Asian (EAS) AF: 0.254 AC: 1309 AN: 5162

South Asian (SAS) AF: 0.495 AC: 2389 AN: 4824

European-Finnish (FIN) AF: 0.472 AC: 4987 AN: 10556

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36261 AN: 67964

Other (OTH) AF: 0.476 AC: 999 AN: 2100

Alfa AF: 0.513 Hom.: 77278

Bravo AF: 0.477

Asia WGS AF: 0.333 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.8
DANN	Benign	0.86
PhyloP100		-0.28
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: rs1558875; hg19: chr17-66344416;