9-19050164-C-T

Variant names:

• chr9-19050164-C-T
• NM_006570.5:c.505C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006570.5(RRAGA):​c.505C>T​(p.Leu169Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RRAGA NM_006570.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.61

Genes affected

RRAGA (HGNC:16963): (Ras related GTP binding A) Enables several functions, including GTP binding activity; protein dimerization activity; and ubiquitin protein ligase binding activity. Involved in several processes, including cellular response to amino acid starvation; negative regulation of autophagy; and positive regulation of TORC1 signaling. Located in lysosome and nucleus. Colocalizes with GATOR1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.939

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRAGA	NM_006570.5	c.505C>T	p.Leu169Phe	missense_variant	Exon 1 of 1	ENST00000380527.3	NP_006561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRAGA	ENST00000380527.3	c.505C>T	p.Leu169Phe	missense_variant	Exon 1 of 1	6	NM_006570.5	ENSP00000369899.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 31, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.505C>T (p.L169F) alteration is located in exon 1 (coding exon 1) of the RRAGA gene. This alteration results from a C to T substitution at nucleotide position 505, causing the leucine (L) at amino acid position 169 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Benign	0.68	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.56	D
MutationAssessor	Pathogenic	4.0	H
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.7	D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.85		Gain of loop (P = 0.069);
MVP		0.91
MPC		2.6
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.99
gMVP		0.96

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-19050162;