17-8393096-C-T

Variant names:

• chr17-8393096-C-T
• rs1200010478
• NM_001146684.3:c.366G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001146684.3(RNF222):​c.366G>A​(p.Gln122Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000739 in 1,353,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: RNF222 NM_001146684.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-0.076 with no splicing effect.

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.366G>A	p.Gln122Gln	synonymous	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.366G>A	p.Gln122Gln	synonymous	Exon 3 of 3	ENSP00000382330.1	A6NCQ9
	RNF222	ENST00000344001.3	TSL:6	c.366G>A	p.Gln122Gln	synonymous	Exon 1 of 1	ENSP00000343799.3	A6NCQ9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000931 AC: 1 AN: 107358 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000259

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.39e-7 AC: 1 AN: 1353652 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 664118

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30600

American (AMR) AF: 0.00 AC: 0 AN: 30954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22080

East Asian (EAS) AF: 0.00 AC: 0 AN: 35446

South Asian (SAS) AF: 0.00 AC: 0 AN: 72872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5392

European-Non Finnish (NFE) AF: 9.44e-7 AC: 1 AN: 1059838

Other (OTH) AF: 0.00 AC: 0 AN: 56078

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.54
PhyloP100		-0.076
PromoterAI		-0.010	Neutral

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: rs1200010478; hg19: chr17-8296414;