chr19-11399893-G-A

Variant names:

• chr19-11399893-G-A
• rs779188410
• NM_001035223.4:c.1708C>T

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.1708C>T​(p.Pro570Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000102 in 1,368,218 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: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: RGL3 NM_001035223.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.80
• Publications: 2 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=0.17078197).

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.1708C>T	p.Pro570Ser	missense	Exon 16 of 19	NP_001030300.3	Q3MIN7-1
	RGL3	NM_001161616.3		c.1726C>T	p.Pro576Ser	missense	Exon 16 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.1708C>T	p.Pro570Ser	missense	Exon 16 of 19	ENSP00000369823.3	Q3MIN7-1
	RGL3	ENST00000393423.7	TSL:1	c.1726C>T	p.Pro576Ser	missense	Exon 16 of 19	ENSP00000377075.3	Q3MIN7-2
	RGL3	ENST00000920283.1		c.1747C>T	p.Pro583Ser	missense	Exon 16 of 19	ENSP00000590342.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000168 AC: 3 AN: 178964 AF XY: 0.0000308

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000102 AC: 14 AN: 1368218 Hom.: 0 Cov.: 31 AF XY: 0.0000163 AC XY: 11 AN XY: 672928

African (AFR) AF: 0.00 AC: 0 AN: 29382

American (AMR) AF: 0.00 AC: 0 AN: 26674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21370

East Asian (EAS) AF: 0.00 AC: 0 AN: 36866

South Asian (SAS) AF: 0.000167 AC: 12 AN: 71648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5386

European-Non Finnish (NFE) AF: 9.35e-7 AC: 1 AN: 1069914

Other (OTH) AF: 0.0000178 AC: 1 AN: 56244

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000495 AC: 6

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	0.076
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.0024	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.8
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.18
Sift	Benign	0.64	T
Sift4G	Benign	0.94	T
Vest4		0.33
MutPred		0.27		Gain of phosphorylation at P570 (P = 0.0019)
MVP		0.56
MPC		0.11
ClinPred		0.20	T
GERP RS		4.9
gMVP		0.50
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs779188410; hg19: chr19-11510569;