1-68047001-GCG-CAA

Variant names:

• chr1-68047001-GCG-CAA
• NM_004675.5:c.295_297delCGCinsTTG
• DIRAS3 p.Arg99Leu

Variant summary

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

The NM_004675.5(DIRAS3):​c.295_297delCGCinsTTG​(p.Arg99Leu) variant causes a missense change. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DIRAS3 NM_004675.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.10
• Publications: 0 publications found

Genes affected

DIRAS3 (HGNC:687): (DIRAS family GTPase 3) This gene encodes a member of the ras superfamily. This gene is imprinted gene with monoallelic expression of the paternal allele which is associated with growth suppression. The encoded protein acts as a tumor suppressor whose function is abrogated in many ovarian and breast cancers. This protein may also play a role autophagy in certain cancer cells by regulating the autophagosome initiation complex. [provided by RefSeq, Nov 2015]

GNG12-AS1 (HGNC:43938): (GNG12, DIRAS3 and WLS antisense RNA 1)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004675.5. 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
	DIRAS3	NM_004675.5	MANE Select	c.295_297delCGCinsTTG	p.Arg99Leu	missense	N/A	NP_004666.1	O95661
	GNG12-AS1	NR_040077.1		n.266+12238_266+12240delGCGinsCAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIRAS3	ENST00000646789.1	MANE Select	c.295_297delCGCinsTTG	p.Arg99Leu	missense	N/A	ENSP00000495736.1	O95661
	DIRAS3	ENST00000370981.3	TSL:2	c.295_297delCGCinsTTG	p.Arg99Leu	missense	N/A	ENSP00000360020.1	O95661
	DIRAS3	ENST00000691269.1		c.295_297delCGCinsTTG	p.Arg99Leu	missense	N/A	ENSP00000509833.1	O95661

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		6.1

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: chr1-68512684;