3-48964947-G-A

Variant names:

• chr3-48964947-G-A
• rs527850935
• NM_006321.4:c.352G>A

Variant summary

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

The NM_006321.4(ARIH2):​c.352G>A​(p.Val118Ile) 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. 14/22 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. V118F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARIH2 NM_006321.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.47
• Publications: 0 publications found

Genes affected

ARIH2 (HGNC:690): (ariadne RBR E3 ubiquitin protein ligase 2) The protein encoded by this gene is an E3 ubiquitin-protein ligase that polyubiquitinates some proteins, tagging them for degradation. The encoded protein upregulates p53 in some cancer cells and may inhibit myelopoiesis. Several transcript variants encoding different isoforms have been found for this gene, although the full-length nature of some of them have not been determined yet. [provided by RefSeq, Nov 2015]

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=0.15628213).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006321.4. 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
	ARIH2	NM_006321.4	MANE Select	c.352G>A	p.Val118Ile	missense	Exon 5 of 16	NP_006312.1	Q6IBL8
	ARIH2	NM_001349213.2		c.352G>A	p.Val118Ile	missense	Exon 6 of 17	NP_001336142.1
	ARIH2	NM_001349214.2		c.352G>A	p.Val118Ile	missense	Exon 5 of 16	NP_001336143.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARIH2	ENST00000356401.9	TSL:1 MANE Select	c.352G>A	p.Val118Ile	missense	Exon 5 of 16	ENSP00000348769.4	O95376
	ARIH2	ENST00000449376.5	TSL:1	c.352G>A	p.Val118Ile	missense	Exon 6 of 17	ENSP00000403222.1	O95376
	ARIH2	ENST00000972221.1		c.352G>A	p.Val118Ile	missense	Exon 6 of 18	ENSP00000642280.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251370 AF XY: 0.00

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.063
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	-0.41	N
PhyloP100		6.5
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.13
Sift	Benign	0.29	T
Sift4G	Benign	0.73	T
Polyphen		0.0050	B
Vest4		0.34
MutPred		0.45		Loss of disorder (P = 0.1307)
MVP		0.55
MPC		0.54
ClinPred		0.42	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.049
gMVP		0.16
Mutation Taster		=91/9	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: rs527850935; hg19: chr3-49002380;