5-159161472-C-G

Variant names:

• chr5-159161472-C-G
• NM_001199383.2:c.1420G>C

Variant summary

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

The NM_001199383.2(RNF145):​c.1420G>C​(p.Val474Leu) variant causes a missense change. 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: RNF145 NM_001199383.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.94

Genes affected

RNF145 (HGNC:20853): (ring finger protein 145) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [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 rank	MANE	Protein	UniProt
RNF145	NM_001199383.2	c.1420G>C	p.Val474Leu	missense_variant	Exon 10 of 11	ENST00000424310.7	NP_001186312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF145	ENST00000424310.7	c.1420G>C	p.Val474Leu	missense_variant	Exon 10 of 11	1	NM_001199383.2	ENSP00000409064.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1510G>C (p.V504L) alteration is located in exon 10 (coding exon 10) of the RNF145 gene. This alteration results from a G to C substitution at nucleotide position 1510, causing the valine (V) at amino acid position 504 to be replaced by a leucine (L). 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	0.29
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	.;T;T;T;.;.;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D;.;.;D;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.64	D;D;D;D;D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.69	.;N;N;N;.;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.86	N;N;N;.;.;N;N
REVEL	Uncertain	0.41
Sift	Benign	0.20	T;T;T;.;.;T;T
Sift4G	Benign	0.13	T;T;T;T;T;T;T
Polyphen		0.90	P;P;P;P;.;.;.
Vest4		0.69
MutPred		0.53		.;Loss of glycosylation at S475 (P = 0.1124);Loss of glycosylation at S475 (P = 0.1124);Loss of glycosylation at S475 (P = 0.1124);.;.;.;
MVP		0.91
MPC		1.4
ClinPred		0.59	D
GERP RS		5.7
Varity_R		0.21
gMVP		0.79

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: chr5-158588480;