12-47748851-GCC-TCT

Variant names:

• chr12-47748851-GCC-TCT
• NM_001098531.4:c.1120_1122delGGCinsAGA
• RAPGEF3 p.Gly374Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001098531.4(RAPGEF3):​c.1120_1122delGGCinsAGA​(p.Gly374Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAPGEF3 NM_001098531.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 0 publications found

Genes affected

RAPGEF3 (HGNC:16629): (Rap guanine nucleotide exchange factor 3) Enables guanyl-nucleotide exchange factor activity and protein domain specific binding activity. Involved in several processes, including positive regulation of protein modification process; regulation of actin cytoskeleton organization; and regulation of syncytium formation by plasma membrane fusion. Located in filopodium; lamellipodium; and microvillus. Colocalizes with cortical actin cytoskeleton and plasma membrane. Biomarker of congestive heart failure. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098531.4. 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
	RAPGEF3	NM_001098531.4	MANE Select	c.1120_1122delGGCinsAGA	p.Gly374Arg	missense	N/A	NP_001092001.2	O95398-1
	RAPGEF3	NM_001098532.2		c.994_996delGGCinsAGA	p.Gly332Arg	missense	N/A	NP_001092002.1	O95398
	RAPGEF3	NM_006105.5		c.994_996delGGCinsAGA	p.Gly332Arg	missense	N/A	NP_006096.2	Q99777

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF3	ENST00000449771.7	TSL:2 MANE Select	c.1120_1122delGGCinsAGA	p.Gly374Arg	missense	N/A	ENSP00000395708.2	O95398-1
	RAPGEF3	ENST00000389212.7	TSL:2	c.1120_1122delGGCinsAGA	p.Gly374Arg	missense	N/A	ENSP00000373864.3	O95398-1
	RAPGEF3	ENST00000549151.5	TSL:5	c.994_996delGGCinsAGA	p.Gly332Arg	missense	N/A	ENSP00000448619.1	O95398-3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-48142634;