NM_006570.5:c.914G>T

Variant names:

• chr9-19050573-G-T
• NM_006570.5:c.914G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006570.5(RRAGA):​c.914G>T​(p.Gly305Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.34
• Publications: 0 publications found

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]

RRAGA Gene-Disease associations (from GenCC):

• cataract

  Inheritance: AD Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006570.5. 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
	RRAGA	NM_006570.5	MANE Select	c.914G>T	p.Gly305Val	missense	Exon 1 of 1	NP_006561.1	Q7L523

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRAGA	ENST00000380527.3	TSL:6 MANE Select	c.914G>T	p.Gly305Val	missense	Exon 1 of 1	ENSP00000369899.1	Q7L523

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.088
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.048
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.3
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.23
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.12	T
Polyphen		0.089	B
Vest4		0.66
MutPred		0.18		Loss of disorder (P = 0.0693)
MVP		0.74
MPC		1.7
ClinPred		0.94	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.51
gMVP		0.68
Mutation Taster		=48/52	disease causing

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

hg19: chr9-19050571;