1-44412576-G-T

Variant names:

• chr1-44412576-G-T
• rs746015309
• NM_018150.4:c.479G>T

Variant summary

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

The NM_018150.4(RNF220):​c.479G>T​(p.Gly160Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 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. G160D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RNF220 NM_018150.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60

Genes affected

RNF220 (HGNC:25552): (ring finger protein 220) Predicted to enable ubiquitin protein ligase activity. Involved in positive regulation of canonical Wnt signaling pathway. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF220	NM_018150.4	c.479G>T	p.Gly160Val	missense_variant	Exon 2 of 15	ENST00000361799.7	NP_060620.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF220	ENST00000361799.7	c.479G>T	p.Gly160Val	missense_variant	Exon 2 of 15	1	NM_018150.4	ENSP00000354872.2
RNF220	ENST00000355387.6	c.479G>T	p.Gly160Val	missense_variant	Exon 2 of 15	1		ENSP00000347548.2
RNF220	ENST00000470498.1	n.-122G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251486 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135916

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T;T;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	.;.;T
M_CAP	Benign	0.0071	T
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.81	L;L;L
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.9	N;N;N
REVEL	Uncertain	0.37
Sift	Uncertain	0.012	D;D;D
Sift4G	Benign	0.17	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.79
MutPred		0.29		Gain of methylation at K161 (P = 0.0427);Gain of methylation at K161 (P = 0.0427);Gain of methylation at K161 (P = 0.0427);
MVP		0.37
MPC		2.0
ClinPred		0.77	D
GERP RS		5.7
Varity_R		0.39
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs746015309; hg19: chr1-44878248;