chr1-44412396-C-T

Position:

• chr1-44412396-C-T

Variant summary

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

The NM_018150.4(RNF220):​c.299C>T​(p.Ala100Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.38

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/exons	MANE	Protein	UniProt
RNF220	NM_018150.4	c.299C>T	p.Ala100Val	missense_variant	2/15	ENST00000361799.7	NP_060620.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF220	ENST00000361799.7	c.299C>T	p.Ala100Val	missense_variant	2/15	1	NM_018150.4	ENSP00000354872	P1
RNF220	ENST00000355387.6	c.299C>T	p.Ala100Val	missense_variant	2/15	1		ENSP00000347548	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2023

The c.299C>T (p.A100V) alteration is located in exon 2 (coding exon 1) of the RNF220 gene. This alteration results from a C to T substitution at nucleotide position 299, causing the alanine (A) at amino acid position 100 to be replaced by a valine (V). 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	0.20
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.030	T;T;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;.;D
M_CAP	Benign	0.0041	T
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.69	N;N;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.50	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.031	D;D;D
Sift4G	Uncertain	0.052	T;T;T
Polyphen		0.99	D;D;D
Vest4		0.82
MutPred		0.29		Loss of disorder (P = 0.0888);Loss of disorder (P = 0.0888);Loss of disorder (P = 0.0888);
MVP		0.15
MPC		1.1
ClinPred		0.93	D
GERP RS		5.9
Varity_R		0.097
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr1-44878068;