chr5-159158885-G-C

Variant names:

• chr5-159158885-G-C
• NM_001199383.2:c.1777C>G

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.1777C>G​(p.Leu593Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RNF145 NM_001199383.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90
• Publications: 0 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=0.07372582).

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.1777C>G	p.Leu593Val	missense	Exon 11 of 11	NP_001186312.1	Q96MT1-1
	RNF145	NM_001199380.2		c.1867C>G	p.Leu623Val	missense	Exon 11 of 11	NP_001186309.1	Q96MT1-5
	RNF145	NM_144726.3		c.1861C>G	p.Leu621Val	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.1777C>G	p.Leu593Val	missense	Exon 11 of 11	ENSP00000409064.2	Q96MT1-1
	RNF145	ENST00000518802.5	TSL:1	c.1867C>G	p.Leu623Val	missense	Exon 11 of 11	ENSP00000430955.1	Q96MT1-5
	RNF145	ENST00000274542.6	TSL:2	c.1861C>G	p.Leu621Val	missense	Exon 11 of 11	ENSP00000274542.2	Q96MT1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461670 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727146

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111840

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.43
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.9
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.13
Sift	Benign	0.29	T
Sift4G	Benign	1.0	T
Polyphen		0.0050	B
Vest4		0.015
MutPred		0.29		Loss of helix (P = 0.1299)
MVP		0.44
MPC		0.022
ClinPred		0.034	T
GERP RS		3.4
Varity_R		0.027
gMVP		0.11
Mutation Taster		=98/2	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

hg19: chr5-158585893;