chr5-64213643-C-G

Position:

• chr5-64213643-C-G

Variant summary

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

The NM_001113561.2(RNF180):​c.317C>G​(p.Ser106Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF180 NM_001113561.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.53

Genes affected

RNF180 (HGNC:27752): (ring finger protein 180) Predicted to enable ubiquitin conjugating enzyme binding activity and ubiquitin protein ligase activity. Predicted to be involved in norepinephrine metabolic process; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; and serotonin metabolic process. Predicted to act upstream of or within several processes, including adult behavior; positive regulation of protein ubiquitination; and protein polyubiquitination. Predicted to be located in nuclear envelope. Predicted to be integral component of membrane. Predicted to be intrinsic component of endoplasmic reticulum membrane. [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
RNF180	NM_001113561.2	c.317C>G	p.Ser106Cys	missense_variant	4/8	ENST00000389100.9	NP_001107033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF180	ENST00000389100.9	c.317C>G	p.Ser106Cys	missense_variant	4/8	1	NM_001113561.2	ENSP00000373752.4
RNF180	ENST00000296615.10	c.317C>G	p.Ser106Cys	missense_variant	4/5	1		ENSP00000296615.6
RNF180	ENST00000504296.1	c.317C>G	p.Ser106Cys	missense_variant	4/4	3		ENSP00000426884.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Dec 10, 2024

The c.317C>G (p.S106C) alteration is located in exon 4 (coding exon 3) of the RNF180 gene. This alteration results from a C to G substitution at nucleotide position 317, causing the serine (S) at amino acid position 106 to be replaced by a cysteine (C). 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	0.12
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T;.
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.010	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.72
MutPred		0.62		Gain of ubiquitination at K104 (P = 0.1008);Gain of ubiquitination at K104 (P = 0.1008);Gain of ubiquitination at K104 (P = 0.1008);
MVP		0.90
MPC		0.040
ClinPred		0.94	D
GERP RS		6.1
Varity_R		0.15
gMVP		0.45

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: chr5-63509470;