rs556658999

Variant names:

• chr17-8393235-C-T
• rs556658999
• NM_001146684.3:c.227G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-8393235-C-T
• chr17-8393235-C-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001146684.3(RNF222):​c.227G>A​(p.Arg76His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000038 in 1,551,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R76C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: RNF222 NM_001146684.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.357
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034276694).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146684.3. 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
	RNF222	NM_001146684.3	MANE Select	c.227G>A	p.Arg76His	missense	Exon 3 of 3	NP_001140156.1	A6NCQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF222	ENST00000399398.3	TSL:5 MANE Select	c.227G>A	p.Arg76His	missense	Exon 3 of 3	ENSP00000382330.1	A6NCQ9
	RNF222	ENST00000344001.3	TSL:6	c.227G>A	p.Arg76His	missense	Exon 1 of 1	ENSP00000343799.3	A6NCQ9

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000820

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000459 AC: 7 AN: 152394 AF XY: 0.0000492

Gnomad AFR exome AF: 0.000662

Gnomad AMR exome AF: 0.0000811

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000136 AC: 19 AN: 1398716 Hom.: 0 Cov.: 34 AF XY: 0.0000174 AC XY: 12 AN XY: 689886

African (AFR) AF: 0.000348 AC: 11 AN: 31598

American (AMR) AF: 0.0000560 AC: 2 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000463 AC: 5 AN: 1078964

Other (OTH) AF: 0.0000172 AC: 1 AN: 58000

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152286 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74468

African (AFR) AF: 0.000818 AC: 34 AN: 41562

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000496 Hom.: 0

Bravo AF: 0.000261

ExAC AF: 0.0000385 AC: 1

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	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0033	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.36
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.050
Sift	Benign	0.14	T
Sift4G	Benign	0.57	T
Polyphen		0.99	D
Vest4		0.077
MVP		0.055
ClinPred		0.10	T
GERP RS		4.4
PromoterAI		-0.0032	Neutral
Varity_R		0.11
gMVP		0.30
Mutation Taster		=92/8	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: rs556658999; hg19: chr17-8296553;