chr13-113979409-C-T

Variant names:

• chr13-113979409-C-T
• rs148918325
• NM_007368.4:c.2443G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_007368.4(RASA3):​c.2443G>A​(p.Gly815Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000258 in 1,601,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: RASA3 NM_007368.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.75
• Publications: 0 publications found

Genes affected

RASA3 (HGNC:20331): (RAS p21 protein activator 3) This gene encodes a protein that binds inositol 1,3,4,5-tetrakisphosphate and stimulates the GTPase activity of Ras p21. This protein functions as a negative regulator of the Ras signalling pathway. It is localized to the cell membrane via a pleckstrin homology (PH) domain in the C-terminal region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.858

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007368.4. 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
	RASA3	NM_007368.4	MANE Select	c.2443G>A	p.Gly815Arg	missense	Exon 24 of 24	NP_031394.2
	RASA3	NM_001320822.2		c.2347G>A	p.Gly783Arg	missense	Exon 24 of 24	NP_001307751.1	Q14644-2
	RASA3	NM_001320821.2		c.1294G>A	p.Gly432Arg	missense	Exon 26 of 26	NP_001307750.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASA3	ENST00000334062.8	TSL:1 MANE Select	c.2443G>A	p.Gly815Arg	missense	Exon 24 of 24	ENSP00000335029.7	Q14644-1
	RASA3	ENST00000947917.1		c.2833G>A	p.Gly945Arg	missense	Exon 25 of 25	ENSP00000617976.1
	RASA3	ENST00000881265.1		c.2533G>A	p.Gly845Arg	missense	Exon 24 of 24	ENSP00000551324.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152218 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000229 AC: 57 AN: 248714 AF XY: 0.000171

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000463

Gnomad NFE exome AF: 0.000306

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000270 AC: 391 AN: 1449192 Hom.: 0 Cov.: 30 AF XY: 0.000241 AC XY: 174 AN XY: 721662

African (AFR) AF: 0.000151 AC: 5 AN: 33150

American (AMR) AF: 0.000134 AC: 6 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39640

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85986

European-Finnish (FIN) AF: 0.000621 AC: 33 AN: 53146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.000300 AC: 330 AN: 1100764

Other (OTH) AF: 0.000200 AC: 12 AN: 59974

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152218 Hom.: 0 Cov.: 34 AF XY: 0.000148 AC XY: 11 AN XY: 74360

African (AFR) AF: 0.0000723 AC: 3 AN: 41468

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000267 Hom.: 0

Bravo AF: 0.000162

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000272 AC: 33

EpiCase AF: 0.000218

EpiControl AF: 0.000178

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	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.74	D
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Pathogenic	0.50	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.70	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.7
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.30		Gain of solvent accessibility (P = 0.0042)
MVP		0.94
MPC		1.3
ClinPred		0.68	D
GERP RS		4.8
Varity_R		0.44
gMVP		0.84
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs148918325; hg19: chr13-114748820;