chr1-44412417-C-G

Variant names:

• chr1-44412417-C-G
• NM_018150.4:c.320C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018150.4(RNF220):​c.320C>G​(p.Thr107Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF220 NM_018150.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.69

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08448359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF220	NM_018150.4	c.320C>G	p.Thr107Ser	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.320C>G	p.Thr107Ser	missense_variant	Exon 2 of 15	1	NM_018150.4	ENSP00000354872.2
RNF220	ENST00000355387.6	c.320C>G	p.Thr107Ser	missense_variant	Exon 2 of 15	1		ENSP00000347548.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.320C>G (p.T107S) alteration is located in exon 2 (coding exon 1) of the RNF220 gene. This alteration results from a C to G substitution at nucleotide position 320, causing the threonine (T) at amino acid position 107 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Benign	0.75
DEOGEN2	Benign	0.017	T;T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	0.058
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	.;.;T
M_CAP	Benign	0.00088	T
MetaRNN	Benign	0.084	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.29	N;N;N
REVEL	Benign	0.10
Sift	Benign	0.69	T;T;T
Sift4G	Benign	0.65	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.12
MutPred		0.22		Gain of disorder (P = 0.0313);Gain of disorder (P = 0.0313);Gain of disorder (P = 0.0313);
MVP		0.068
MPC		0.65
ClinPred		0.38	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.086
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-44878089;