chr1-44626312-G-A

Position:

• chr1-44626312-G-A

Variant summary

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

The NM_018150.4(RNF220):​c.820G>A​(p.Ala274Thr) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RNF220 NM_018150.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.07

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=0.11602387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF220	NM_018150.4	c.820G>A	p.Ala274Thr	missense_variant	5/15	ENST00000361799.7	NP_060620.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF220	ENST00000361799.7	c.820G>A	p.Ala274Thr	missense_variant	5/15	1	NM_018150.4	ENSP00000354872	P1
RNF220	ENST00000355387.6	c.820G>A	p.Ala274Thr	missense_variant	5/15	1		ENSP00000347548	P1
RNF220	ENST00000496262.1	n.95G>A		non_coding_transcript_exon_variant	3/3	2
RNF220	ENST00000453863.5			upstream_gene_variant		3		ENSP00000411541

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2021

The c.820G>A (p.A274T) alteration is located in exon 5 (coding exon 4) of the RNF220 gene. This alteration results from a G to A substitution at nucleotide position 820, causing the alanine (A) at amino acid position 274 to be replaced by a threonine (T). 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	0.094
BayesDel_addAF	Benign	-0.0070	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T;T;T
Eigen	Benign	0.031
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;.;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Uncertain	-0.066	T
MutationAssessor	Benign	0.69	N;N;N
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.070	N;N;N
REVEL	Benign	0.19
Sift	Benign	0.22	T;T;T
Sift4G	Benign	0.45	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.077
MutPred		0.18		Gain of glycosylation at A274 (P = 0.0453);Gain of glycosylation at A274 (P = 0.0453);Gain of glycosylation at A274 (P = 0.0453);
MVP		0.27
MPC		0.74
ClinPred		0.77	D
GERP RS		4.4
Varity_R		0.088
gMVP		0.55

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-45091984;