6-89380239-T-G

Position:

• chr6-89380239-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021244.5(RRAGD):​c.573A>C​(p.Glu191Asp) variant causes a missense 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. 14/21 in silico tools predict 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: 32)
• Consequence: RRAGD NM_021244.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61

Genes affected

RRAGD (HGNC:19903): (Ras related GTP binding D) RRAGD is a monomeric guanine nucleotide-binding protein, or G protein. By binding GTP or GDP, small G proteins act as molecular switches in numerous cell processes and signaling pathways.[supplied by OMIM, Apr 2004]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1978623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRAGD	NM_021244.5	c.573A>C	p.Glu191Asp	missense_variant	3/7	ENST00000369415.9	NP_067067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRAGD	ENST00000369415.9	c.573A>C	p.Glu191Asp	missense_variant	3/7	1	NM_021244.5	ENSP00000358423.4
RRAGD	ENST00000359203.3	c.120A>C	p.Glu40Asp	missense_variant	2/6	2		ENSP00000352131.2
RRAGD	ENST00000492783.1	n.597A>C		non_coding_transcript_exon_variant	3/5	5

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

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.573A>C (p.E191D) alteration is located in exon 3 (coding exon 3) of the RRAGD gene. This alteration results from a A to C substitution at nucleotide position 573, causing the glutamic acid (E) at amino acid position 191 to be replaced by an aspartic acid (D). 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	Benign	0.29
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Benign	0.51
DEOGEN2	Benign	0.27	T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.27	N;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.29
Sift	Benign	0.97	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;.
Vest4		0.46
MutPred		0.52		Gain of phosphorylation at T192 (P = 0.1777);.;
MVP		0.65
MPC		0.69
ClinPred		0.42	T
GERP RS		5.8
Varity_R		0.41
gMVP		0.70

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: chr6-90089958;