Variant 10-43198035-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145313.4(RASGEF1A):c.1193A>G(p.Asn398Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Consequence

RASGEF1A
NM_145313.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20853981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RASGEF1A	NM_145313.4 linkuse as main transcript	c.1193A>G	p.Asn398Ser	missense_variant	10/13	ENST00000395810.6	NP_660356.2
RASGEF1A	NM_001282862.2 linkuse as main transcript	c.1217A>G	p.Asn406Ser	missense_variant	10/13		NP_001269791.1
RASGEF1A	XM_005271809.4 linkuse as main transcript	c.953A>G	p.Asn318Ser	missense_variant	9/12		XP_005271866.1
RASGEF1A	XM_011539500.3 linkuse as main transcript	c.953A>G	p.Asn318Ser	missense_variant	9/12		XP_011537802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGEF1A	ENST00000395810.6 linkuse as main transcript	c.1193A>G	p.Asn398Ser	missense_variant	10/13	1	NM_145313.4	ENSP00000379155	A1	Q8N9B8-1
RASGEF1A	ENST00000374459.5 linkuse as main transcript	c.1217A>G	p.Asn406Ser	missense_variant	10/13	2		ENSP00000363583	P4	Q8N9B8-2
RASGEF1A	ENST00000395809.5 linkuse as main transcript	c.1193A>G	p.Asn398Ser	missense_variant	10/13	2		ENSP00000379154	A1	Q8N9B8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251226

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Mar 26, 2024

The c.1193A>G (p.N398S) alteration is located in exon 9 (coding exon 9) of the RASGEF1A gene. This alteration results from a A to G substitution at nucleotide position 1193, causing the asparagine (N) at amino acid position 398 to be replaced by a serine (S). 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

0.094

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.68

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

.;T;T

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.85

D;.;D

M_CAP

Benign

0.0064

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.95

.;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Benign

0.13

Sift

Benign

0.036

D;D;D

Sift4G

Benign

0.086

T;T;T

Polyphen

0.57

P;P;P

Vest4

0.23

MutPred

0.53

.;Gain of glycosylation at N398 (P = 0.0452);Gain of glycosylation at N398 (P = 0.0452);

MVP

0.30

MPC

0.93

ClinPred

0.87

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.69

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

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