NM_006570.5:c.-62C>A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006570.5(RRAGA):​c.-62C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,307,996 control chromosomes in the GnomAD database, including 20,739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (5183 hom., cov: 33)
  • Exomes 𝑓: 0.15 (15556 hom.)
• Consequence: RRAGA NM_006570.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.198

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 9-19049598-C-A is Benign according to our data. Variant chr9-19049598-C-A is described in ClinVar as [Benign]. Clinvar id is 1269481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRAGA	NM_006570.5	c.-62C>A		5_prime_UTR_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	c.-62C>A		5_prime_UTR_variant	Exon 1 of 1		NM_006570.5	ENSP00000369899.1
SAXO1	ENST00000542071.2	c.-547G>T		upstream_gene_variant		3		ENSP00000438823.2
SAXO1	ENST00000649457.1	c.-547G>T		upstream_gene_variant				ENSP00000497677.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34384 AN: 152038 Hom.: 5177 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0488

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.155 AC: 179009 AN: 1155840 Hom.: 15556 Cov.: 15 AF XY: 0.155 AC XY: 88505 AN XY: 572610

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.0458

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.226 AC: 34424 AN: 152156 Hom.: 5183 Cov.: 33 AF XY: 0.221 AC XY: 16435 AN XY: 74392

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0486

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.235

Alfa AF: 0.202 Hom.: 504

Bravo AF: 0.238

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.2
DANN	Benign	0.83
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

Publications

LitVar

Other links and lift over

dbSNP: rs2233802; hg19: chr9-19049596;