14-73491097-G-A

Variant names:

• chr14-73491097-G-A
• NM_024644.5:c.80G>A

Variant summary

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

The NM_024644.5(RIOX1):​c.80G>A​(p.Gly27Glu) 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. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RIOX1 NM_024644.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04
• Publications: 0 publications found

Genes affected

RIOX1 (HGNC:20968): (ribosomal oxygenase 1) Predicted to enable histone H3-methyl-lysine-36 demethylase activity; histone H3-methyl-lysine-4 demethylase activity; and iron ion binding activity. Predicted to be involved in histone lysine demethylation; negative regulation of osteoblast differentiation; and negative regulation of transcription, DNA-templated. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

HEATR4 (HGNC:16761): (HEAT repeat containing 4) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACOT1 (HGNC:33128): (acyl-CoA thioesterase 1) Enables acyl-CoA hydrolase activity. Involved in acyl-CoA metabolic process; long-chain fatty acid metabolic process; and very long-chain fatty acid metabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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=0.24497062).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024644.5. 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
	RIOX1	NM_024644.5	MANE Select	c.80G>A	p.Gly27Glu	missense	Exon 1 of 1	NP_078920.2	Q9H6W3-1
	HEATR4	NM_001220484.1	MANE Select	c.2844+1969C>T		intron	N/A	NP_001207413.1	Q86WZ0
	HEATR4	NM_203309.2		c.2844+1969C>T		intron	N/A	NP_976054.2	Q86WZ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIOX1	ENST00000304061.8	TSL:6 MANE Select	c.80G>A	p.Gly27Glu	missense	Exon 1 of 1	ENSP00000477507.1	Q9H6W3-1
	HEATR4	ENST00000553558.6	TSL:2 MANE Select	c.2844+1969C>T		intron	N/A	ENSP00000450444.2	Q86WZ0
	HEATR4	ENST00000334988.2	TSL:1	c.2844+1969C>T		intron	N/A	ENSP00000335447.2	Q86WZ0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1449474 Hom.: 0 Cov.: 83 AF XY: 0.00 AC XY: 0 AN XY: 720524

African (AFR) AF: 0.00 AC: 0 AN: 32562

American (AMR) AF: 0.00 AC: 0 AN: 43152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25912

East Asian (EAS) AF: 0.00 AC: 0 AN: 38958

South Asian (SAS) AF: 0.00 AC: 0 AN: 83912

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106216

Other (OTH) AF: 0.00 AC: 0 AN: 59882

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	20
DANN	Benign	0.76
DEOGEN2	Benign	0.0074	T
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.24	T
PhyloP100		1.0
Sift4G	Benign	0.067	T
Polyphen		0.96	D
Vest4		0.24
MVP		0.23
GERP RS		2.9
PromoterAI		0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.079
gMVP		0.099
Mutation Taster		=100/0	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

hg19: chr14-73957802;