ARSG p.Thr236Ser

Variant names:

• chr17-68368549-A-T
• NM_001267727.2:c.706A>T
• ARSG p.Thr236Ser

Your query was ambiguous. Multiple possible variants found:

• chr17-68368549-A-T
• chr17-68368550-C-G
• chr17-68368549-ACC-TCT
• chr17-68368549-ACC-TCA
• chr17-68368549-ACC-TCG
• chr17-68368550-CC-GT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001267727.2(ARSG):​c.706A>T​(p.Thr236Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ARSG NM_001267727.2 missense, splice_region
• Scores: Splicing: ADA: 0.000008919
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Genomics England PanelApp
• Usher syndrome type 3

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03163764).

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.706A>T	p.Thr236Ser	missense splice_region	Exon 7 of 12	NP_001254656.1	Q96EG1
	ARSG	NM_001352899.2		c.706A>T	p.Thr236Ser	missense splice_region	Exon 7 of 13	NP_001339828.1	Q96EG1
	ARSG	NM_001352900.2		c.706A>T	p.Thr236Ser	missense splice_region	Exon 7 of 12	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.706A>T	p.Thr236Ser	missense splice_region	Exon 7 of 12	ENSP00000480910.1	Q96EG1
	ARSG	ENST00000448504.6	TSL:1	c.706A>T	p.Thr236Ser	missense splice_region	Exon 7 of 12	ENSP00000407193.2	Q96EG1
	ARSG	ENST00000452479.6	TSL:5	c.214A>T	p.Thr72Ser	missense splice_region	Exon 6 of 11	ENSP00000413953.2	J9JIG6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.017
DANN	Benign	0.69
DEOGEN2	Benign	0.28	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.25	N
PhyloP100		-1.4
PrimateAI	Benign	0.30	T
REVEL	Benign	0.012
Sift4G	Benign	0.67	T
Varity_R		0.045
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000089
dbscSNV1_RF	Benign	0.012
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-66364690;