chr11-72693325-CC-TT

Variant names:

• chr11-72693325-CC-TT
• NM_001040118.3:c.3953_3954delGGinsAA
• ARAP1 p.Arg1318Gln

Variant summary

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

The NM_001040118.3(ARAP1):​c.3953_3954delGGinsAA​(p.Arg1318Gln) variant causes a missense, splice region 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1318W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARAP1 NM_001040118.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.19
• Publications: 0 publications found

Genes affected

ARAP1 (HGNC:16925): (ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1) The protein encoded by this gene contains SAM, ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology (PH) domains. In vitro, this protein displays RHO-GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent ARF-GAP activity. The encoded protein associates with the Golgi, and the ARF-GAP activity mediates changes in the Golgi and the formation of filopodia. It is thought to regulate the cell-specific trafficking of a receptor protein involved in apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ARAP1-AS1 (HGNC:39993): (ARAP1 antisense RNA 1)

ENSG00000286555 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040118.3. 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
	ARAP1	NM_001040118.3	MANE Select	c.3953_3954delGGinsAA	p.Arg1318Gln	missense splice_region	N/A	NP_001035207.1	Q96P48-6
	ARAP1	NM_015242.5		c.3218_3219delGGinsAA	p.Arg1073Gln	missense splice_region	N/A	NP_056057.2	Q96P48-4
	ARAP1	NM_001369489.1		c.3218_3219delGGinsAA	p.Arg1073Gln	missense splice_region	N/A	NP_001356418.1	E7EU13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARAP1	ENST00000393609.8	TSL:2 MANE Select	c.3953_3954delGGinsAA	p.Arg1318Gln	missense splice_region	N/A	ENSP00000377233.3	Q96P48-6
	ARAP1	ENST00000393605.7	TSL:1	c.3233_3234delGGinsAA	p.Arg1078Gln	missense splice_region	N/A	ENSP00000377230.3	Q96P48-1
	ARAP1	ENST00000334211.12	TSL:1	c.3218_3219delGGinsAA	p.Arg1073Gln	missense splice_region	N/A	ENSP00000335506.8	Q96P48-4

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		7.2

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: chr11-72404370;