NM_001669.4:c.1321G>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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=0.1821982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSD	NM_001669.4	c.1321G>A	p.Val441Ile	missense_variant	Exon 9 of 10	ENST00000381154.6	NP_001660.2
ARSD	XM_005274514.3	c.1186G>A	p.Val396Ile	missense_variant	Exon 8 of 9		XP_005274571.1
ARSD	XM_047442108.1	c.1183G>A	p.Val395Ile	missense_variant	Exon 9 of 10		XP_047298064.1
ARSD	XM_005274515.3	c.1321G>A	p.Val441Ile	missense_variant	Exon 9 of 10		XP_005274572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSD	ENST00000381154.6	c.1321G>A	p.Val441Ile	missense_variant	Exon 9 of 10	1	NM_001669.4	ENSP00000370546.1
ARSD	ENST00000458014.1	c.127G>A	p.Val43Ile	missense_variant	Exon 2 of 4	3		ENSP00000409180.1
ARSD	ENST00000495294.1	n.119-15G>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.10	N;N
REVEL	Benign	0.23
Sift	Benign	0.077	T;T
Sift4G	Benign	0.11	T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs775107418; hg19: chrX-2826861;