NM_001011719.2:c.329C>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001011719.2(ARSH):​c.329C>T​(p.Thr110Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000914 in 1,094,367 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 21)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

ARSH
NM_001011719.2 missense

Scores

8
8
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.65
Variant links:
Genes affected
ARSH (HGNC:32488): (arylsulfatase family member H) Sulfatases, such as ARSH, hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules (Sardiello et al., 2005 [PubMed 16174644]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.964

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARSHNM_001011719.2 linkc.329C>T p.Thr110Met missense_variant Exon 3 of 9 ENST00000381130.3 NP_001011719.1 Q5FYA8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARSHENST00000381130.3 linkc.329C>T p.Thr110Met missense_variant Exon 3 of 9 1 NM_001011719.2 ENSP00000370522.3 Q5FYA8

Frequencies

GnomAD3 genomes
Cov.:
21
GnomAD4 exome
AF:
9.14e-7
AC:
1
AN:
1094367
Hom.:
0
Cov.:
30
AF XY:
0.00000278
AC XY:
1
AN XY:
359955
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000335
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.75
D
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.95
D
M_CAP
Pathogenic
0.69
D
MetaRNN
Pathogenic
0.96
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
4.0
H
PrimateAI
Uncertain
0.63
T
PROVEAN
Pathogenic
-5.7
D
REVEL
Pathogenic
0.84
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.0080
D
Polyphen
1.0
D
Vest4
0.56
MutPred
0.83
Loss of catalytic residue at T110 (P = 0.053);
MVP
0.61
MPC
0.64
ClinPred
0.99
D
GERP RS
3.3
Varity_R
0.48
gMVP
0.95

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: rs753484979; hg19: chrX-2931202; COSMIC: COSV105930223; API