rs553759260

Variant names:

• chr5-180128418-C-A
• rs553759260
• NM_175062.4:c.631G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-180128418-C-A
• chr5-180128418-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_175062.4(RASGEF1C):​c.631G>T​(p.Val211Leu) 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 1,461,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. V211M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RASGEF1C NM_175062.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3150742).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175062.4. 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
	RASGEF1C	NM_175062.4	MANE Select	c.631G>T	p.Val211Leu	missense	Exon 5 of 14	NP_778232.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGEF1C	ENST00000361132.9	TSL:1 MANE Select	c.631G>T	p.Val211Leu	missense	Exon 5 of 14	ENSP00000354963.4	Q8N431-1
	RASGEF1C	ENST00000393371.6	TSL:1	c.631G>T	p.Val211Leu	missense	Exon 4 of 13	ENSP00000377037.2	Q8N431-1
	RASGEF1C	ENST00000923269.1		c.631G>T	p.Val211Leu	missense	Exon 6 of 15	ENSP00000593328.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461194 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 726906

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5328

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111924

Other (OTH) AF: 0.00 AC: 0 AN: 60328

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.23	N
PhyloP100		1.3
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.077
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.081	T
Polyphen		0.60	P
Vest4		0.36
MutPred		0.45		Gain of disorder (P = 0.237)
MVP		0.34
MPC		0.41
ClinPred		0.79	D
GERP RS		2.5
Varity_R		0.24
gMVP		0.54
Mutation Taster		=81/19	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: rs553759260; hg19: chr5-179555418;