rs777437516

Variant names:

• chr13-113981721-C-A
• rs777437516
• NM_007368.4:c.2383G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-113981721-C-A
• chr13-113981721-C-T

Variant summary

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

The NM_007368.4(RASA3):​c.2383G>T​(p.Ala795Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A795T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: RASA3 NM_007368.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25081336).

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.2383G>T	p.Ala795Ser	missense	Exon 23 of 24	NP_031394.2
	RASA3	NM_001320822.2		c.2287G>T	p.Ala763Ser	missense	Exon 23 of 24	NP_001307751.1	Q14644-2
	RASA3	NM_001320821.2		c.1234G>T	p.Ala412Ser	missense	Exon 25 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.2383G>T	p.Ala795Ser	missense	Exon 23 of 24	ENSP00000335029.7	Q14644-1
	RASA3	ENST00000947917.1		c.2773G>T	p.Ala925Ser	missense	Exon 24 of 25	ENSP00000617976.1
	RASA3	ENST00000881265.1		c.2473G>T	p.Ala825Ser	missense	Exon 23 of 24	ENSP00000551324.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461784 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 727198

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

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

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111970

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	0.0038	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.010
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.25
Sift	Benign	0.41	T
Sift4G	Benign	0.30	T
Polyphen		0.10	B
Vest4		0.42
MutPred		0.21		Gain of helix (P = 0.062)
MVP		0.85
MPC		0.54
ClinPred		0.57	D
GERP RS		4.9
Varity_R		0.085
gMVP		0.30
Mutation Taster		=86/14	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

dbSNP: rs777437516; hg19: chr13-114751132;