17-8393096-C-G

Variant names:

• chr17-8393096-C-G
• NM_001146684.3:c.366G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001146684.3(RNF222):​c.366G>C​(p.Gln122His) 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. 14/19 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)
• Consequence: RNF222 NM_001146684.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0760

Genes affected

RNF222 (HGNC:34517): (ring finger protein 222) Predicted to enable metal ion binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12824532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF222	NM_001146684.3	c.366G>C	p.Gln122His	missense_variant	Exon 3 of 3	ENST00000399398.3	NP_001140156.1
RNF222	XM_011523978.4	c.366G>C	p.Gln122His	missense_variant	Exon 3 of 3		XP_011522280.1
RNF222	XM_011523980.4	c.366G>C	p.Gln122His	missense_variant	Exon 2 of 2		XP_011522282.1
RNF222	XM_011523981.4	c.366G>C	p.Gln122His	missense_variant	Exon 2 of 2		XP_011522283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF222	ENST00000399398.3	c.366G>C	p.Gln122His	missense_variant	Exon 3 of 3	5	NM_001146684.3	ENSP00000382330.1
RNF222	ENST00000344001.3	c.366G>C	p.Gln122His	missense_variant	Exon 1 of 1	6		ENSP00000343799.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.366G>C (p.Q122H) alteration is located in exon 3 (coding exon 1) of the RNF222 gene. This alteration results from a G to C substitution at nucleotide position 366, causing the glutamine (Q) at amino acid position 122 to be replaced by a histidine (H). 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	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.7
DANN	Benign	0.97
DEOGEN2	Benign	0.0016	T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.42	T;.
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.42	N;N
REVEL	Benign	0.18
Sift	Benign	0.035	D;D
Sift4G	Benign	0.57	T;T
Polyphen		0.88	P;P
Vest4		0.20
MutPred		0.25		Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);
MVP		0.014
ClinPred		0.31	T
GERP RS		2.1
Varity_R		0.052
gMVP		0.31

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-8296414;