NM_001011719.2:c.563G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001011719.2(ARSH):​c.563G>T​(p.Arg188Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,556 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 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)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

ARSH
NM_001011719.2 missense

Scores

3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.302
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]

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ACMG classification

Classification made for transcript

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=0.2624918).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARSHNM_001011719.2 linkc.563G>T p.Arg188Leu missense_variant Exon 4 of 9 ENST00000381130.3 NP_001011719.1 Q5FYA8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARSHENST00000381130.3 linkc.563G>T p.Arg188Leu missense_variant Exon 4 of 9 1 NM_001011719.2 ENSP00000370522.3 Q5FYA8

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
9.12e-7
AC:
1
AN:
1096556
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
362084
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:
0.0000186
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
22
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.088
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
14
DANN
Benign
0.96
DEOGEN2
Uncertain
0.55
D
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.38
T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.26
T
MetaSVM
Uncertain
-0.27
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.19
T
PROVEAN
Uncertain
-3.5
D
REVEL
Benign
0.27
Sift
Benign
0.18
T
Sift4G
Benign
0.30
T
Polyphen
0.70
P
Vest4
0.12
MutPred
0.64
Loss of MoRF binding (P = 0.01);
MVP
0.18
MPC
0.28
ClinPred
0.51
D
GERP RS
3.0
Varity_R
0.16
gMVP
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs142811205; hg19: chrX-2933233; API