rs1367860884

Variant names:

• chr1-44649887-C-G
• rs1367860884
• NM_018150.4:c.1559C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-44649887-C-G
• chr1-44649887-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP2

The NM_018150.4(RNF220):​c.1559C>G​(p.Ser520Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S520L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF220 NM_018150.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.56
• Publications: 0 publications found

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]

TMEM53 (HGNC:26186): (transmembrane protein 53) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TMEM53 Gene-Disease associations (from GenCC):

• craniotubular dysplasia, Ikegawa type

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• skeletal dysplasia

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

LOC107984950 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 2 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 2.2243 (below the threshold of 3.09). Trascript score misZ: 2.8161 (below the threshold of 3.09). GenCC associations: The gene is linked to leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018150.4. 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
	RNF220	NM_018150.4	MANE Select	c.1559C>G	p.Ser520Trp	missense	Exon 14 of 15	NP_060620.2
	RNF220	NM_001376486.1		c.1637C>G	p.Ser546Trp	missense	Exon 14 of 15	NP_001363415.1
	RNF220	NM_001376487.1		c.1637C>G	p.Ser546Trp	missense	Exon 14 of 15	NP_001363416.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF220	ENST00000361799.7	TSL:1 MANE Select	c.1559C>G	p.Ser520Trp	missense	Exon 14 of 15	ENSP00000354872.2	Q5VTB9-1
	RNF220	ENST00000355387.6	TSL:1	c.1559C>G	p.Ser520Trp	missense	Exon 14 of 15	ENSP00000347548.2	Q5VTB9-1
	RNF220	ENST00000925767.1		c.1562C>G	p.Ser521Trp	missense	Exon 14 of 15	ENSP00000595826.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	0.66	D
MutationAssessor	Benign	1.5	L
PhyloP100		7.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.8	D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.45		Gain of catalytic residue at M523 (P = 0.008)
MVP		0.90
MPC		2.1
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.44
gMVP		0.91
Mutation Taster		=40/60	disease causing

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: rs1367860884; hg19: chr1-45115559;