15-78991778-GC-CT

Variant names:

• chr15-78991778-GC-CT
• NM_001145648.3:c.3043_3044delGCinsAG
• RASGRF1 p.Ala1015Ser

Variant summary

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

The NM_001145648.3(RASGRF1):​c.3043_3044delGCinsAG​(p.Ala1015Ser) variant causes a missense change involving the alteration of a 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1015T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RASGRF1 NM_001145648.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.48
• Publications: 0 publications found

Genes affected

RASGRF1 (HGNC:9875): (Ras protein specific guanine nucleotide releasing factor 1) The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) similar to the Saccharomyces cerevisiae CDC25 gene product. Functional analysis has demonstrated that this protein stimulates the dissociation of GDP from RAS protein. The studies of the similar gene in mouse suggested that the Ras-GEF activity of this protein in brain can be activated by Ca2+ influx, muscarinic receptors, and G protein beta-gamma subunit. Mouse studies also indicated that the Ras-GEF signaling pathway mediated by this protein may be important for long-term memory. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Mar 2009]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145648.3. 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
	RASGRF1	NM_001145648.3	MANE Select	c.3043_3044delGCinsAG	p.Ala1015Ser	missense	N/A	NP_001139120.1	Q13972-3
	RASGRF1	NM_002891.6		c.3091_3092delGCinsAG	p.Ala1031Ser	missense	N/A	NP_002882.3
	RASGRF1	NM_153815.3		c.739_740delGCinsAG	p.Ala247Ser	missense	N/A	NP_722522.1	Q13972-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRF1	ENST00000558480.7	TSL:2 MANE Select	c.3043_3044delGCinsAG	p.Ala1015Ser	missense	N/A	ENSP00000452781.2	Q13972-3
	RASGRF1	ENST00000394745.3	TSL:1	c.739_740delGCinsAG	p.Ala247Ser	missense	N/A	ENSP00000378228.3	Q13972-2
	RASGRF1	ENST00000560334.5	TSL:1	n.2913_2914delGCinsAG		non_coding_transcript_exon	Exon 20 of 24

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		7.5

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: chr15-79284120;