Genetic Variant ARSG:c.1091+896T>C (chr17-68386068-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001267727.2(ARSG):c.1091+896T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,178 control chromosomes in the GnomAD database, including 5,239 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 0.18 ( 5239 hom., cov: 31)

Consequence

ARSG
NM_001267727.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.748

Publications

18 publications found

Variant links:

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

ARSG links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARSG	NM_001267727.2	MANE Select	c.1091+896T>C	intron	N/A	NP_001254656.1	Q96EG1
ARSG	NM_001352899.2		c.1091+896T>C	intron	N/A	NP_001339828.1	Q96EG1
ARSG	NM_001352900.2		c.1091+896T>C	intron	N/A	NP_001339829.1	Q96EG1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARSG	ENST00000621439.5	TSL:5 MANE Select	c.1091+896T>C	intron	N/A	ENSP00000480910.1	Q96EG1
ARSG	ENST00000448504.6	TSL:1	c.1091+896T>C	intron	N/A	ENSP00000407193.2	Q96EG1
ARSG	ENST00000452479.6	TSL:5	c.599+896T>C	intron	N/A	ENSP00000413953.2	J9JIG6

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27969

AN:

152060

Hom.:

5223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.448

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0964

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.464

Gnomad SAS

AF:

0.258

Gnomad FIN

AF:

0.0273

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.0466

Gnomad OTH

AF:

0.167

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

GnomAD4 genome

AF:

0.184

AC:

28026

AN:

152178

Hom.:

5239

Cov.:

AF XY:

0.187

AC XY:

13884

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.448

AC:

18585

AN:

41482

American (AMR)

AF:

0.0962

AC:

1472

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

437

AN:

3472

East Asian (EAS)

AF:

0.465

AC:

2401

AN:

5166

South Asian (SAS)

AF:

0.259

AC:

1247

AN:

4812

European-Finnish (FIN)

AF:

0.0273

AC:

290

AN:

10630

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0466

AC:

3169

AN:

67998

Other (OTH)

AF:

0.166

AC:

351

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

907

1815

2722

3630

4537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.117

Hom.:

4388

Bravo

AF:

0.200

Asia WGS

AF:

0.331

AC:

1150

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

(source)

DANN

Benign

0.50

PhyloP100

0.75

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over