X-2908820-C-T

Variant names:

• chrX-2908820-C-T
• rs775107418
• NM_001669.4:c.1321G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001669.4(ARSD):​c.1321G>A​(p.Val441Ile) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V441L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: ARSD NM_001669.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1821982).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001669.4. 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
	ARSD	NM_001669.4	MANE Select	c.1321G>A	p.Val441Ile	missense	Exon 9 of 10	NP_001660.2	P51689-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSD	ENST00000381154.6	TSL:1 MANE Select	c.1321G>A	p.Val441Ile	missense	Exon 9 of 10	ENSP00000370546.1	P51689-1
	ARSD	ENST00000954947.1		c.1186G>A	p.Val396Ile	missense	Exon 8 of 9	ENSP00000625006.1
	ARSD	ENST00000954948.1		c.886G>A	p.Val296Ile	missense	Exon 6 of 7	ENSP00000625007.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.43
DANN	Benign	0.93
DEOGEN2	Benign	0.16	T
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.19
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.23
Sift	Benign	0.077	T
Sift4G	Benign	0.11	T
Polyphen		0.0090	B
Vest4		0.036
MutPred		0.54		Gain of catalytic residue at V441 (P = 0.1307)
MVP		0.44
MPC		0.13
ClinPred		0.30	T
GERP RS		-3.6
Varity_R		0.057
gMVP		0.41
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs775107418; hg19: chrX-2826861;