5-159161595-A-G

Variant names:

• chr5-159161595-A-G
• rs540581579
• NM_001199383.2:c.1297T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001199383.2(RNF145):​c.1297T>C​(p.Leu433Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RNF145 NM_001199383.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=2.92 with no splicing effect.

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.1297T>C	p.Leu433Leu	synonymous	Exon 10 of 11	NP_001186312.1	Q96MT1-1
	RNF145	NM_001199380.2		c.1387T>C	p.Leu463Leu	synonymous	Exon 10 of 11	NP_001186309.1	Q96MT1-5
	RNF145	NM_144726.3		c.1381T>C	p.Leu461Leu	synonymous	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.1297T>C	p.Leu433Leu	synonymous	Exon 10 of 11	ENSP00000409064.2	Q96MT1-1
	RNF145	ENST00000518802.5	TSL:1	c.1387T>C	p.Leu463Leu	synonymous	Exon 10 of 11	ENSP00000430955.1	Q96MT1-5
	RNF145	ENST00000274542.6	TSL:2	c.1381T>C	p.Leu461Leu	synonymous	Exon 10 of 11	ENSP00000274542.2	Q96MT1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450752 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 721468

African (AFR) AF: 0.00 AC: 0 AN: 32786

American (AMR) AF: 0.00 AC: 0 AN: 42100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25626

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.00 AC: 0 AN: 84278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107388

Other (OTH) AF: 0.0000167 AC: 1 AN: 59900

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.7
DANN	Benign	0.79
PhyloP100		2.9

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: rs540581579; hg19: chr5-158588603;