1-1072043-C-A

Variant names:

• chr1-1072043-C-A
• rs542538552
• NM_001205252.2:c.524G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001205252.2(RNF223):​c.524G>T​(p.Arg175Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000045 in 1,332,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. R175Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: RNF223 NM_001205252.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056652665).

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.524G>T	p.Arg175Leu	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.524G>T	p.Arg175Leu	missense	Exon 2 of 2	ENSP00000410533.1	E7ERA6
	ENSG00000304169	ENST00000800220.1		n.98-617C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000450 AC: 6 AN: 1332838 Hom.: 0 Cov.: 37 AF XY: 0.00000305 AC XY: 2 AN XY: 656742

African (AFR) AF: 0.00 AC: 0 AN: 26350

American (AMR) AF: 0.00 AC: 0 AN: 28482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23098

East Asian (EAS) AF: 0.00 AC: 0 AN: 32302

South Asian (SAS) AF: 0.00 AC: 0 AN: 71766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5500

European-Non Finnish (NFE) AF: 0.00000568 AC: 6 AN: 1056956

Other (OTH) AF: 0.00 AC: 0 AN: 55410

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.51
DANN	Benign	0.78
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.34	T
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.0	N
PhyloP100		-0.013
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.14
Sift	Benign	0.40	T
Sift4G	Benign	0.26	T
Vest4		0.024
MutPred		0.27		Loss of solvent accessibility (P = 0.0022)
MVP		0.35
ClinPred		0.044	T
GERP RS		-2.8
Varity_R		0.026
gMVP		0.29
Mutation Taster		=99/1	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: rs542538552; hg19: chr1-1007423;