5-38945513-C-T

Variant names:

• chr5-38945513-C-T
• rs144269248
• NM_152756.5:c.4611G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_152756.5(RICTOR):​c.4611G>A​(p.Leu1537Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L1537L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RICTOR NM_152756.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 0 publications found

Genes affected

RICTOR (HGNC:28611): (RPTOR independent companion of MTOR complex 2) RICTOR and MTOR (FRAP1; MIM 601231) are components of a protein complex that integrates nutrient- and growth factor-derived signals to regulate cell growth (Sarbassov et al., 2004 [PubMed 15268862]).[supplied by OMIM, Mar 2008]

OSMR (HGNC:8507): (oncostatin M receptor) This gene encodes a member of the type I cytokine receptor family. The encoded protein heterodimerizes with interleukin 6 signal transducer to form the type II oncostatin M receptor and with interleukin 31 receptor A to form the interleukin 31 receptor, and thus transduces oncostatin M and interleukin 31 induced signaling events. Mutations in this gene have been associated with familial primary localized cutaneous amyloidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

OSMR Gene-Disease associations (from GenCC):

• amyloidosis, primary localized cutaneous, 1

  Inheritance: AD, SD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial primary localized cutaneous amyloidosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=-0.113 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152756.5. 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
	RICTOR	NM_152756.5	MANE Select	c.4611G>A	p.Leu1537Leu	synonymous	Exon 34 of 38	NP_689969.2
	RICTOR	NM_001285439.2		c.4683G>A	p.Leu1561Leu	synonymous	Exon 35 of 39	NP_001272368.1	Q6R327-3
	RICTOR	NM_001438246.1		c.4635G>A	p.Leu1545Leu	synonymous	Exon 34 of 38	NP_001425175.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RICTOR	ENST00000357387.8	TSL:1 MANE Select	c.4611G>A	p.Leu1537Leu	synonymous	Exon 34 of 38	ENSP00000349959.3	Q6R327-1
	RICTOR	ENST00000296782.10	TSL:1	c.4683G>A	p.Leu1561Leu	synonymous	Exon 35 of 39	ENSP00000296782.5	Q6R327-3
	RICTOR	ENST00000511516.5	TSL:1	n.*3721G>A		non_coding_transcript_exon	Exon 34 of 38	ENSP00000423019.1	Q6R327-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	4.8
DANN	Benign	0.72
PhyloP100		-0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs144269248; hg19: chr5-38945615;