3-97949876-G-C

Position:

• chr3-97949876-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153182.4(RIOX2):​c.1028C>G​(p.Ser343Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: RIOX2 NM_153182.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.250

Genes affected

RIOX2 (HGNC:19441): (ribosomal oxygenase 2) MINA is a c-Myc (MYC; MIM 190080) target gene that may play a role in cell proliferation or regulation of cell growth. (Tsuneoka et al., 2002 [PubMed 12091391]; Zhang et al., 2005 [PubMed 15897898]).[supplied by OMIM, May 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061975002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIOX2	NM_153182.4	c.1028C>G	p.Ser343Cys	missense_variant	7/10	ENST00000394198.7	NP_694822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIOX2	ENST00000394198.7	c.1028C>G	p.Ser343Cys	missense_variant	7/10	1	NM_153182.4	ENSP00000377748.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461622 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727110

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000144

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2023

The c.1028C>G (p.S343C) alteration is located in exon 7 (coding exon 6) of the MINA gene. This alteration results from a C to G substitution at nucleotide position 1028, causing the serine (S) at amino acid position 343 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.47
DANN	Benign	0.62
DEOGEN2	Benign	0.022	T;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.38	.;T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.062	T;T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.60	N;N;N
REVEL	Benign	0.0040
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.11
MutPred		0.62		Loss of disorder (P = 0.0045);Loss of disorder (P = 0.0045);.;
MVP		0.081
MPC		0.068
ClinPred		0.036	T
GERP RS		-6.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.049
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs959662016; hg19: chr3-97668720;