5-159158755-C-G

Variant names:

• chr5-159158755-C-G
• rs151308498
• NM_001199383.2:c.1907G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001199383.2(RNF145):​c.1907G>C​(p.Arg636Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. R636L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF145 NM_001199383.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 1 publications found

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]

LINC02202 (HGNC:53068): (long intergenic non-protein coding RNA 2202)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08971378).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199383.2. 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
	RNF145	NM_001199383.2	MANE Select	c.1907G>C	p.Arg636Pro	missense	Exon 11 of 11	NP_001186312.1	Q96MT1-1
	RNF145	NM_001199380.2		c.1997G>C	p.Arg666Pro	missense	Exon 11 of 11	NP_001186309.1	Q96MT1-5
	RNF145	NM_144726.3		c.1991G>C	p.Arg664Pro	missense	Exon 11 of 11	NP_653327.1	Q96MT1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF145	ENST00000424310.7	TSL:1 MANE Select	c.1907G>C	p.Arg636Pro	missense	Exon 11 of 11	ENSP00000409064.2	Q96MT1-1
	RNF145	ENST00000518802.5	TSL:1	c.1997G>C	p.Arg666Pro	missense	Exon 11 of 11	ENSP00000430955.1	Q96MT1-5
	RNF145	ENST00000274542.6	TSL:2	c.1991G>C	p.Arg664Pro	missense	Exon 11 of 11	ENSP00000274542.2	Q96MT1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	0.70
DANN	Benign	0.68
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.078
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.64	N
REVEL	Uncertain	0.34
Sift	Benign	0.26	T
Sift4G	Benign	0.28	T
Polyphen		0.026	B
Vest4		0.22
MutPred		0.23		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.70
MPC		0.027
ClinPred		0.025	T
GERP RS		1.2
Varity_R		0.12
gMVP		0.22
Mutation Taster		=97/3	polymorphism

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: rs151308498; hg19: chr5-158585763;