15-32616326-GCC-ACG

Variant names:

• chr15-32616326-GCC-ACG
• NM_014783.6:c.115_117delGCCinsACG
• ARHGAP11A p.Ala39Thr

Variant summary

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

The NM_014783.6(ARHGAP11A):​c.115_117delGCCinsACG​(p.Ala39Thr) 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ARHGAP11A NM_014783.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.851
• Publications: 0 publications found

Genes affected

ARHGAP11A (HGNC:15783): (Rho GTPase activating protein 11A) This gene encodes a member of the Rho GTPase activating protein family. In response to DNA damage, the encoded protein interacts with the p53 tumor suppressor protein and stimulates its tetramerization, which results in cell-cycle arrest and apoptosis. A chromosomal deletion that includes this gene is one cause of Prader-Willi syndrome, and an intronic variant of this gene may be associated with sleep duration in children. This gene is highly expressed in colon cancers and in a human basal-like breast cancer cell line. This gene also produces a ARHGAP11A-SCG5 readthrough transcript and ARHGAP11A-SCG5 protein. [provided by RefSeq, Feb 2019]

ARHGAP11A-SCG5 (HGNC:56310): (ARHGAP11A-SCG5 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring ARHGAP11A (Rho GTPase activating protein 11A) and SCG5 (secretogranin V) genes on chromosome 15q13.3. The readthrough transcript encodes a fusion protein that shares sequence identity with both the ARHGAP11A and SCG5 gene products. [provided by RefSeq, Feb 2019]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014783.6. 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
	ARHGAP11A	NM_014783.6	MANE Select	c.115_117delGCCinsACG	p.Ala39Thr	missense	N/A	NP_055598.1	Q6P4F7-1
	ARHGAP11A-SCG5	NM_001368319.1		c.115_117delGCCinsACG	p.Ala39Thr	missense	N/A	NP_001355248.1	A0A8I5KWH8
	ARHGAP11A	NM_199357.3		c.115_117delGCCinsACG	p.Ala39Thr	missense	N/A	NP_955389.1	Q6P4F7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP11A	ENST00000361627.8	TSL:1 MANE Select	c.115_117delGCCinsACG	p.Ala39Thr	missense	N/A	ENSP00000355090.3	Q6P4F7-1
	ARHGAP11A-SCG5	ENST00000692248.1		c.115_117delGCCinsACG	p.Ala39Thr	missense	N/A	ENSP00000510771.1	A0A8I5KWH8
	ARHGAP11A	ENST00000567348.5	TSL:1	c.115_117delGCCinsACG	p.Ala39Thr	missense	N/A	ENSP00000454575.1	Q6P4F7-2

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.85

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: chr15-32908527;