Genetic Variant NM_005744.5:c.43G>C (chr15-72474682-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005744.5(ARIH1):c.43G>C(p.Glu15Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E15A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ARIH1
NM_005744.5 missense

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 5.87

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32282934).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005744.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARIH1	NM_005744.5	MANE Select	c.43G>C	p.Glu15Gln	missense	Exon 1 of 14	NP_005735.2	Q9Y4X5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARIH1	ENST00000379887.9	TSL:1 MANE Select	c.43G>C	p.Glu15Gln	missense	Exon 1 of 14	ENSP00000369217.4	Q9Y4X5
ARIH1	ENST00000915026.1		c.43G>C	p.Glu15Gln	missense	Exon 1 of 14	ENSP00000585085.1
ARIH1	ENST00000915024.1		c.43G>C	p.Glu15Gln	missense	Exon 1 of 14	ENSP00000585083.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1422528

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706950

African (AFR)

AF:

0.00

AC:

AN:

30182

American (AMR)

AF:

0.00

AC:

AN:

39910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24952

East Asian (EAS)

AF:

0.00

AC:

AN:

35414

South Asian (SAS)

AF:

0.00

AC:

AN:

81948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51792

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094036

Other (OTH)

AF:

0.00

AC:

AN:

58650

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:association

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Aortic aneurysm (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.32

MetaSVM

Uncertain

0.31

MutationAssessor

Benign

0.34

PhyloP100

5.9

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.22

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.039

Polyphen

0.83

Vest4

0.27

MVP

0.69

MPC

1.1

ClinPred

0.84

GERP RS

3.8

PromoterAI

-0.062

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.64

gMVP

0.14

Mutation Taster

=30/70

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over