X-2910704-T-C

Position:

• chrX-2910704-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001669.4(ARSD):​c.1090A>G​(p.Arg364Gly) variant causes a missense 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ARSD NM_001669.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0780

Genes affected

ARSD (HGNC:717): (arylsulfatase D) The protein encoded by this gene is a member of the sulfatase family. Sulfatases are essential for the correct composition of bone and cartilage matrix. The encoded protein is postranslationally glycosylated and localized to the lysosome. This gene is located within a cluster of similar arylsulfatase genes on chromosome X. A related pseudogene has been identified in the pseudoautosomal region of chromosome Y. [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1619412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSD	NM_001669.4	c.1090A>G	p.Arg364Gly	missense_variant	7/10	ENST00000381154.6	NP_001660.2
ARSD	XM_047442108.1	c.952A>G	p.Arg318Gly	missense_variant	7/10		XP_047298064.1
ARSD	XM_005274515.3	c.1090A>G	p.Arg364Gly	missense_variant	7/10		XP_005274572.1
ARSD	XM_005274514.3	c.1001-725A>G		intron_variant			XP_005274571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSD	ENST00000381154.6	c.1090A>G	p.Arg364Gly	missense_variant	7/10	1	NM_001669.4	ENSP00000370546	P1
ARSD	ENST00000495294.1	n.119-1899A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.1090A>G (p.R364G) alteration is located in exon 7 (coding exon 7) of the ARSD gene. This alteration results from a A to G substitution at nucleotide position 1090, causing the arginine (R) at amino acid position 364 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	13
DANN	Benign	0.61
DEOGEN2	Uncertain	0.69	D
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.31	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.19
Sift	Benign	0.39	T
Sift4G	Benign	0.41	T
Polyphen		0.0090	B
Vest4		0.15
MutPred		0.53		Loss of stability (P = 0.0082);
MVP		0.98
MPC		0.21
ClinPred		0.21	T
GERP RS		-1.7
Varity_R		0.19
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-2828745;