chr19-11397252-C-T

Variant names:

• chr19-11397252-C-T
• NM_001035223.4:c.2006G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001035223.4(RGL3):​c.2006G>A​(p.Gly669Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RGL3 NM_001035223.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.25
• Publications: 0 publications found

Genes affected

RGL3 (HGNC:30282): (ral guanine nucleotide dissociation stimulator like 3) Predicted to enable guanyl-nucleotide exchange factor activity and small GTPase binding activity. Predicted to be involved in positive regulation of GTPase activity and small GTPase mediated signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18859339).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001035223.4. 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
	RGL3	NM_001035223.4	MANE Select	c.2006G>A	p.Gly669Glu	missense	Exon 18 of 19	NP_001030300.3	Q3MIN7-1
	RGL3	NM_001161616.3		c.2024G>A	p.Gly675Glu	missense	Exon 18 of 19	NP_001155088.2	Q3MIN7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGL3	ENST00000380456.8	TSL:1 MANE Select	c.2006G>A	p.Gly669Glu	missense	Exon 18 of 19	ENSP00000369823.3	Q3MIN7-1
	RGL3	ENST00000393423.7	TSL:1	c.2024G>A	p.Gly675Glu	missense	Exon 18 of 19	ENSP00000377075.3	Q3MIN7-2
	RGL3	ENST00000920283.1		c.2045G>A	p.Gly682Glu	missense	Exon 18 of 19	ENSP00000590342.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461566 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727112

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111862

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 31

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	0.12
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Benign	0.75
DEOGEN2	Benign	0.0020	T
Eigen	Benign	0.096
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	0.66	T
Vest4		0.22
MutPred		0.56		Gain of solvent accessibility (P = 0.005)
MVP		0.39
MPC		0.14
ClinPred		0.79	D
GERP RS		4.7
gMVP		0.21
Mutation Taster		=60/40	polymorphism

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: chr19-11507928;