3-48967254-GTC-ATT

Variant names:

• chr3-48967254-GTC-ATT
• NM_006321.4:c.517_519delGTCinsATT
• ARIH2 p.Val173Ile

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_006321.4(ARIH2):​c.517_519delGTCinsATT​(p.Val173Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARIH2 NM_006321.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.54
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.517_519delGTCinsATT	p.Val173Ile	missense	N/A	NP_006312.1	Q6IBL8
	ARIH2	NM_001349213.2		c.517_519delGTCinsATT	p.Val173Ile	missense	N/A	NP_001336142.1
	ARIH2	NM_001349214.2		c.517_519delGTCinsATT	p.Val173Ile	missense	N/A	NP_001336143.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARIH2	ENST00000356401.9	TSL:1 MANE Select	c.517_519delGTCinsATT	p.Val173Ile	missense	N/A	ENSP00000348769.4	O95376
	ARIH2	ENST00000449376.5	TSL:1	c.517_519delGTCinsATT	p.Val173Ile	missense	N/A	ENSP00000403222.1	O95376
	ARIH2	ENST00000972221.1		c.517_519delGTCinsATT	p.Val173Ile	missense	N/A	ENSP00000642280.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-49004687;