NM_001205252.2:c.674G>C

Variant names:

• chr1-1071893-C-G
• rs760536755
• NM_001205252.2:c.674G>C

Variant summary

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

The NM_001205252.2(RNF223):​c.674G>C​(p.Arg225Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,380,596 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R225H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: RNF223 NM_001205252.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249
• Publications: 0 publications found

Genes affected

RNF223 (HGNC:40020): (ring finger protein 223) Predicted to enable metal ion binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000304169 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205252.2. 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
	RNF223	NM_001205252.2	MANE Select	c.674G>C	p.Arg225Pro	missense	Exon 2 of 2	NP_001192181.1	E7ERA6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF223	ENST00000453464.3	TSL:2 MANE Select	c.674G>C	p.Arg225Pro	missense	Exon 2 of 2	ENSP00000410533.1	E7ERA6
	ENSG00000304169	ENST00000800220.1		n.98-767C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1380596 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 681218

African (AFR) AF: 0.00 AC: 0 AN: 31358

American (AMR) AF: 0.00 AC: 0 AN: 35510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25078

East Asian (EAS) AF: 0.00 AC: 0 AN: 35642

South Asian (SAS) AF: 0.00 AC: 0 AN: 78924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5482

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077432

Other (OTH) AF: 0.00 AC: 0 AN: 57748

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	5.7
DANN	Benign	0.96
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.75
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.43	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.25
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.54
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0050	D
Vest4		0.47
MutPred		0.38		Loss of sheet (P = 0.0228)
MVP		0.39
ClinPred		0.58	D
GERP RS		-4.0
Varity_R		0.18
gMVP		0.59
Mutation Taster		=78/22	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: rs760536755; hg19: chr1-1007273;