rs78142040

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_009589.5(ARSD):​c.1044G>A​(p.Ala348Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 913,840 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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: not found (cov: 23)
Exomes 𝑓: 0.0000055 ( 0 hom. 1 hem. )

Consequence

ARSD
NM_009589.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.02).
BP7
Synonymous conserved (PhyloP=-1.15 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARSDNM_001669.4 linkc.1000+826G>A intron_variant Intron 6 of 9 ENST00000381154.6 NP_001660.2 P51689-1A0A140VK06

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARSDENST00000381154.6 linkc.1000+826G>A intron_variant Intron 6 of 9 1 NM_001669.4 ENSP00000370546.1 P51689-1
ARSDENST00000217890.10 linkn.1044G>A non_coding_transcript_exon_variant Exon 7 of 7 1
ARSDENST00000481340.1 linkn.119G>A non_coding_transcript_exon_variant Exon 2 of 2 3
ARSDENST00000495294.1 linkn.119-5925G>A intron_variant Intron 1 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.00000547
AC:
5
AN:
913840
Hom.:
0
Cov.:
30
AF XY:
0.00000333
AC XY:
1
AN XY:
300708
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000193
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000414
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23
Alfa
AF:
0.128
Hom.:
0
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.060
DANN
Benign
0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs78142040; hg19: chrX-2832771; COSMIC: COSV54200115; COSMIC: COSV54200115; API