chr5-159161405-T-C

Variant names:

• chr5-159161405-T-C
• rs1237176495
• NM_001199383.2:c.1487A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001199383.2(RNF145):​c.1487A>G​(p.Tyr496Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: RNF145 NM_001199383.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 32 AD gene.

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.1487A>G	p.Tyr496Cys	missense	Exon 10 of 11	NP_001186312.1	Q96MT1-1
	RNF145	NM_001199380.2		c.1577A>G	p.Tyr526Cys	missense	Exon 10 of 11	NP_001186309.1	Q96MT1-5
	RNF145	NM_144726.3		c.1571A>G	p.Tyr524Cys	missense	Exon 10 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.1487A>G	p.Tyr496Cys	missense	Exon 10 of 11	ENSP00000409064.2	Q96MT1-1
	RNF145	ENST00000518802.5	TSL:1	c.1577A>G	p.Tyr526Cys	missense	Exon 10 of 11	ENSP00000430955.1	Q96MT1-5
	RNF145	ENST00000274542.6	TSL:2	c.1571A>G	p.Tyr524Cys	missense	Exon 10 of 11	ENSP00000274542.2	Q96MT1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251480 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 32 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.00

EpiControl AF: 0.000119

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	0.28
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.020
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.34	N
PhyloP100		7.9
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.55
Sift	Benign	0.066	T
Sift4G	Benign	0.13	T
Polyphen		0.057	B
Vest4		0.90
MutPred		0.53		Loss of MoRF binding (P = 0.0903)
MVP		0.88
MPC		2.0
ClinPred		0.43	T
GERP RS		6.1
Varity_R		0.36
gMVP		0.93
Mutation Taster		=25/75	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1237176495; hg19: chr5-158588413;