15-72474808-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4

The NM_005744.5(ARIH1):c.169G>C(p.Glu57Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000047 in 1,488,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

ARIH1
NM_005744.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.23

Variant links:

Genes affected

ARIH1 (HGNC:689): (ariadne RBR E3 ubiquitin protein ligase 1) Enables enzyme binding activity; ubiquitin-protein transferase activity; and zinc ion binding activity. Involved in protein ubiquitination. Located in Lewy body; cytoplasm; and nuclear body. Colocalizes with cullin-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ARIH1 links:

TMEM202-AS1 (HGNC:53265): (TMEM202 antisense RNA 1)

TMEM202-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP2

Missense variant where missense usually causes diseases, ARIH1

BP4

Computational evidence support a benign effect (MetaRNN=0.2657737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARIH1	NM_005744.5 linkuse as main transcript	c.169G>C	p.Glu57Gln	missense_variant	1/14	ENST00000379887.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ARIH1	ENST00000379887.9 linkuse as main transcript	c.169G>C	p.Glu57Gln	missense_variant	1/14	1	NM_005744.5	P1
ARIH1	ENST00000564062.1 linkuse as main transcript	c.166G>C	p.Glu56Gln	missense_variant	1/4	3
TMEM202-AS1	ENST00000565181.1 linkuse as main transcript	n.361C>G		non_coding_transcript_exon_variant	1/1
ARIH1	ENST00000570085.5 linkuse as main transcript	c.169G>C	p.Glu57Gln	missense_variant, NMD_transcript_variant	1/5	3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000449

AC:

AN:

1336414

Hom.:

Cov.:

AF XY:

0.00000454

AC XY:

AN XY:

661508

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:

0.00

Gnomad4 FIN exome

AF:

0.0000204

Gnomad4 NFE exome

AF:

0.00000191

Gnomad4 OTH exome

AF:

0.0000368

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151944

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Aug 09, 2022

This variant has not been reported in the literature in individuals affected with ARIH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 57 of the ARIH1 protein (p.Glu57Gln). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.20

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.023

Eigen

Benign

-0.11

Eigen_PC

Benign

0.047

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.27

MetaSVM

Uncertain

-0.037

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.86

REVEL

Benign

0.19

Sift

Benign

0.037

Sift4G

Benign

0.11

Polyphen

0.028

Vest4

0.20

MutPred

0.26

Loss of solvent accessibility (P = 0.0703);

MVP

0.55

MPC

1.1

ClinPred

0.58

GERP RS

3.9

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

Varity_R

0.29

gMVP

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over