Genetic Variant NM_005744.5:c.116C>A (chr15-72474755-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005744.5(ARIH1):c.116C>A(p.Thr39Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000642 in 1,401,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T39I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

ARIH1
NM_005744.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43

Publications

2 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04541114).

BS2

High AC in GnomAdExome4 at 9 AD gene.

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.116C>A	p.Thr39Asn	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.116C>A	p.Thr39Asn	missense	Exon 1 of 14	ENSP00000369217.4	Q9Y4X5
ARIH1	ENST00000915026.1		c.116C>A	p.Thr39Asn	missense	Exon 1 of 14	ENSP00000585085.1
ARIH1	ENST00000915024.1		c.116C>A	p.Thr39Asn	missense	Exon 1 of 14	ENSP00000585083.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000344

AC:

AN:

203768

AF XY:

0.0000356

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000333

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000642

AC:

AN:

1401264

Hom.:

Cov.:

AF XY:

0.00000860

AC XY:

AN XY:

697354

show subpopulations

African (AFR)

AF:

0.0000344

AC:

AN:

29030

American (AMR)

AF:

0.00

AC:

AN:

37530

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24196

East Asian (EAS)

AF:

0.00

AC:

AN:

32850

South Asian (SAS)

AF:

0.00

AC:

AN:

79686

European-Finnish (FIN)

AF:

0.000153

AC:

AN:

52344

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5570

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1082600

Other (OTH)

AF:

0.00

AC:

AN:

57458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.016

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.55

PhyloP100

1.4

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.020

REVEL

Benign

0.15

Sift

Benign

0.56

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.066

MVP

0.24

MPC

1.2

ClinPred

0.065

GERP RS

2.7

PromoterAI

0.052

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.055

gMVP

0.046

Mutation Taster

=97/3

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over