rs1410762395

Variant names:

• chr5-180127673-C-A
• NM_175062.4:c.650G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-180127673-C-A
• chr5-180127673-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_175062.4(RASGEF1C):​c.650G>T​(p.Arg217Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R217Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RASGEF1C NM_175062.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95

Genes affected

RASGEF1C (HGNC:27400): (RasGEF domain family member 1C) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity and small GTPase mediated signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28985333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGEF1C	NM_175062.4	c.650G>T	p.Arg217Leu	missense_variant	Exon 6 of 14	ENST00000361132.9	NP_778232.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGEF1C	ENST00000361132.9	c.650G>T	p.Arg217Leu	missense_variant	Exon 6 of 14	1	NM_175062.4	ENSP00000354963.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460504 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726568

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T;.;T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	.;D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.77	N;.;N;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.5	N;.;N;N
REVEL	Benign	0.098
Sift	Uncertain	0.0010	D;.;D;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		0.049	B;.;B;.
Vest4		0.41
MutPred		0.52		Loss of disorder (P = 0.1614);.;Loss of disorder (P = 0.1614);.;
MVP		0.39
MPC		0.54
ClinPred		0.70	D
GERP RS		3.3
Varity_R		0.44
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-179554673; COSMIC: COSV63177819;