rs12945290

Variant names:

• chr17-68382856-T-C
• rs12945290
• NM_001267727.2:c.983-2208T>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.983-2208T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,212 control chromosomes in the GnomAD database, including 1,160 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 0.12 (1160 hom., cov: 32)
• Consequence: ARSG NM_001267727.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 10 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.174 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.983-2208T>C		intron	N/A	NP_001254656.1	Q96EG1
	ARSG	NM_001352899.2		c.983-2208T>C		intron	N/A	NP_001339828.1	Q96EG1
	ARSG	NM_001352900.2		c.983-2208T>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.983-2208T>C		intron	N/A	ENSP00000480910.1	Q96EG1
	ARSG	ENST00000448504.6	TSL:1	c.983-2208T>C		intron	N/A	ENSP00000407193.2	Q96EG1
	ARSG	ENST00000452479.6	TSL:5	c.491-2208T>C		intron	N/A	ENSP00000413953.2	J9JIG6

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17620 AN: 152094 Hom.: 1147 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.0992

Gnomad EAS AF: 0.0955

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0995

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.116 AC: 17656 AN: 152212 Hom.: 1160 Cov.: 32 AF XY: 0.118 AC XY: 8797 AN XY: 74408

African (AFR) AF: 0.119 AC: 4929 AN: 41528

American (AMR) AF: 0.179 AC: 2738 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0992 AC: 344 AN: 3468

East Asian (EAS) AF: 0.0957 AC: 496 AN: 5182

South Asian (SAS) AF: 0.161 AC: 779 AN: 4826

European-Finnish (FIN) AF: 0.109 AC: 1160 AN: 10606

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0995 AC: 6769 AN: 68004

Other (OTH) AF: 0.123 AC: 261 AN: 2114

Alfa AF: 0.113 Hom.: 1782

Bravo AF: 0.123

Asia WGS AF: 0.146 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.67
DANN	Benign	0.73
PhyloP100		-0.51
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: rs12945290; hg19: chr17-66378997;