Variant chr10-43200845-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000395810.6(RASGEF1A):c.503G>A(p.Ser168Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RASGEF1A
ENST00000395810.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81

Variant links:

Genes affected

RASGEF1A (HGNC:24246): (RasGEF domain family member 1A) Enables guanyl-nucleotide exchange factor activity. Involved in cell migration and positive regulation of Ras protein signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

RASGEF1A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059235096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RASGEF1A	NM_145313.4 linkuse as main transcript	c.503G>A	p.Ser168Asn	missense_variant	5/13	ENST00000395810.6	NP_660356.2
RASGEF1A	NM_001282862.2 linkuse as main transcript	c.527G>A	p.Ser176Asn	missense_variant	5/13		NP_001269791.1
RASGEF1A	XM_005271809.4 linkuse as main transcript	c.263G>A	p.Ser88Asn	missense_variant	4/12		XP_005271866.1
RASGEF1A	XM_011539500.3 linkuse as main transcript	c.263G>A	p.Ser88Asn	missense_variant	4/12		XP_011537802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGEF1A	ENST00000395810.6 linkuse as main transcript	c.503G>A	p.Ser168Asn	missense_variant	5/13	1	NM_145313.4	ENSP00000379155	A1	Q8N9B8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461736

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2024

The c.503G>A (p.S168N) alteration is located in exon 4 (coding exon 4) of the RASGEF1A gene. This alteration results from a G to A substitution at nucleotide position 503, causing the serine (S) at amino acid position 168 to be replaced by an asparagine (N). 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

0.067

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.0084

.;T;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.71

T;.;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.059

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

.;N;N

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.36

N;N;N

REVEL

Benign

0.070

Sift

Benign

0.78

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.064

MutPred

0.33

.;Loss of helix (P = 0.079);Loss of helix (P = 0.079);

MVP

0.082

MPC

0.68

ClinPred

0.57

GERP RS

4.2

Varity_R

0.027

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over