rs1164971559

Variant names:

• chr1-38846087-C-A
• rs1164971559
• NM_022157.4:c.900G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-38846087-C-A
• chr1-38846087-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_022157.4(RRAGC):​c.900G>T​(p.Gly300Gly) variant causes a splice region, 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. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G300G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RRAGC NM_022157.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.9941
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.900
• Publications: 0 publications found

Genes affected

RRAGC (HGNC:19902): (Ras related GTP binding C) This gene encodes a member of the GTR/RAG GTP-binding protein family. The encoded protein is a monomeric guanine nucleotide-binding protein which forms a heterodimer with RRAGA and RRAGB and is primarily localized to the cytoplasm. The encoded protein promotes intracellular localization of the mTOR complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

RRAGC Gene-Disease associations (from GenCC):

• Long-Olsen-Distelmaier syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P

ENSG00000273637 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022157.4. 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
	RRAGC	NM_022157.4	MANE Select	c.900G>T	p.Gly300Gly	splice_region synonymous	Exon 6 of 7	NP_071440.1	Q9HB90
	RRAGC	NM_001271851.2		c.798G>T	p.Gly266Gly	splice_region synonymous	Exon 6 of 7	NP_001258780.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRAGC	ENST00000373001.4	TSL:1 MANE Select	c.900G>T	p.Gly300Gly	splice_region synonymous	Exon 6 of 7	ENSP00000362092.3	Q9HB90
	RRAGC	ENST00000865050.1		c.642G>T	p.Arg214Ser	missense splice_region	Exon 4 of 5	ENSP00000535109.1
	RRAGC	ENST00000865048.1		c.921G>T	p.Gly307Gly	splice_region synonymous	Exon 6 of 7	ENSP00000535107.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.89
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.24		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1164971559; hg19: chr1-39311759;