10-43198035-T-C

Variant names:

• chr10-43198035-T-C
• rs778899545
• NM_145313.4:c.1193A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.34
• Publications: 0 publications found

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]

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=0.20853981).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145313.4. 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
	RASGEF1A	NM_145313.4	MANE Select	c.1193A>G	p.Asn398Ser	missense	Exon 10 of 13	NP_660356.2	Q8N9B8-1
	RASGEF1A	NM_001282862.2		c.1217A>G	p.Asn406Ser	missense	Exon 10 of 13	NP_001269791.1	Q8N9B8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGEF1A	ENST00000395810.6	TSL:1 MANE Select	c.1193A>G	p.Asn398Ser	missense	Exon 10 of 13	ENSP00000379155.1	Q8N9B8-1
	RASGEF1A	ENST00000954344.1		c.1229A>G	p.Asn410Ser	missense	Exon 10 of 13	ENSP00000624403.1
	RASGEF1A	ENST00000374459.5	TSL:2	c.1217A>G	p.Asn406Ser	missense	Exon 10 of 13	ENSP00000363583.1	Q8N9B8-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251226 AF XY: 0.00000736

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

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	0.094
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.68
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L
PhyloP100		2.3
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.13
Sift	Benign	0.036	D
Sift4G	Benign	0.086	T
Polyphen		0.57	P
Vest4		0.23
MutPred		0.53		Gain of glycosylation at N398 (P = 0.0452)
MVP		0.30
MPC		0.93
ClinPred		0.87	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.69
Mutation Taster		=70/30	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: rs778899545; hg19: chr10-43693483;