rs779981165

Variant names:

• chr15-72474683-A-C
• rs779981165
• NM_005744.5:c.44A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-72474683-A-C
• chr15-72474683-A-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_005744.5(ARIH1):​c.44A>C​(p.Glu15Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000703 in 1,422,944 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E15Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: ARIH1 NM_005744.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2739681).
• BS2: High AC in GnomAdExome4 at 10 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.44A>C	p.Glu15Ala	missense	Exon 1 of 14	NP_005735.2	Q9Y4X5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARIH1	ENST00000379887.9	TSL:1 MANE Select	c.44A>C	p.Glu15Ala	missense	Exon 1 of 14	ENSP00000369217.4	Q9Y4X5
	ARIH1	ENST00000915026.1		c.44A>C	p.Glu15Ala	missense	Exon 1 of 14	ENSP00000585085.1
	ARIH1	ENST00000915024.1		c.44A>C	p.Glu15Ala	missense	Exon 1 of 14	ENSP00000585083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000196 AC: 4 AN: 204504 AF XY: 0.00000892

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: 0.00

Gnomad NFE exome AF: 0.0000433

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000703 AC: 10 AN: 1422944 Hom.: 0 Cov.: 31 AF XY: 0.00000566 AC XY: 4 AN XY: 707248

African (AFR) AF: 0.00 AC: 0 AN: 30156

American (AMR) AF: 0.00 AC: 0 AN: 40034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24972

East Asian (EAS) AF: 0.00 AC: 0 AN: 35404

South Asian (SAS) AF: 0.00 AC: 0 AN: 82006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 0.00000914 AC: 10 AN: 1094206

Other (OTH) AF: 0.00 AC: 0 AN: 58678

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000249 AC: 3

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	0.16	D
MutationAssessor	Benign	0.34	N
PhyloP100		5.5
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.10	N
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.032	D
Polyphen		0.46	P
Vest4		0.34
MutPred		0.12		Loss of solvent accessibility (P = 0.0111)
MVP		0.66
MPC		1.1
ClinPred		0.52	D
GERP RS		3.8
PromoterAI		-0.076	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.52
gMVP		0.16
Mutation Taster		=48/52	disease causing

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

Other links and lift over

dbSNP: rs779981165; hg19: chr15-72767024;