9-19049598-C-G

Variant names:

• chr9-19049598-C-G
• rs2233802
• NM_006570.5:c.-62C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006570.5(RRAGA):​c.-62C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000864 in 1,157,328 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: 33)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: RRAGA NM_006570.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• 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]

SAXO1 (HGNC:28566): (stabilizer of axonemal microtubules 1) Enables microtubule binding activity. Involved in several processes, including cold acclimation; positive regulation of cilium assembly; and protein stabilization. Located in microtubule cytoskeleton and sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

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.-62C>G		5_prime_UTR	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.-62C>G		5_prime_UTR	Exon 1 of 1	ENSP00000369899.1	Q7L523
	SAXO1	ENST00000542071.2	TSL:3	c.-547G>C		upstream_gene	N/A	ENSP00000438823.2	F6S232
	SAXO1	ENST00000649457.1		c.-547G>C		upstream_gene	N/A	ENSP00000497677.1	F6S232

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.64e-7 AC: 1 AN: 1157328 Hom.: 0 Cov.: 15 AF XY: 0.00000174 AC XY: 1 AN XY: 573314

African (AFR) AF: 0.00 AC: 0 AN: 26214

American (AMR) AF: 0.00 AC: 0 AN: 26816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19424

East Asian (EAS) AF: 0.00 AC: 0 AN: 34892

South Asian (SAS) AF: 0.00 AC: 0 AN: 66216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4834

European-Non Finnish (NFE) AF: 0.00000113 AC: 1 AN: 885286

Other (OTH) AF: 0.00 AC: 0 AN: 49208

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.3
DANN	Benign	0.67
PhyloP100		0.20
PromoterAI		-0.050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2233802; hg19: chr9-19049596;