chr15-72474716-A-C

Variant names:

• chr15-72474716-A-C
• rs2140386460
• NM_005744.5:c.77A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005744.5(ARIH1):​c.77A>C​(p.Glu26Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. E26V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARIH1 NM_005744.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22315893).

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.77A>C	p.Glu26Ala	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.77A>C	p.Glu26Ala	missense	Exon 1 of 14	ENSP00000369217.4	Q9Y4X5
	ARIH1	ENST00000915026.1		c.77A>C	p.Glu26Ala	missense	Exon 1 of 14	ENSP00000585085.1
	ARIH1	ENST00000915024.1		c.77A>C	p.Glu26Ala	missense	Exon 1 of 14	ENSP00000585083.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.10
BayesDel_addAF	Benign	-0.0080	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.96	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.6
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.26
Sift	Benign	0.69	T
Sift4G	Benign	0.63	T
Polyphen		0.46	P
Vest4		0.31
MutPred		0.14		Loss of solvent accessibility (P = 0.0435)
MVP		0.68
MPC		1.1
ClinPred		0.52	D
GERP RS		3.9
PromoterAI		-0.049	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.056
Mutation Taster		=69/31	polymorphism

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: rs2140386460; hg19: chr15-72767057;