chr15-32624234-T-G
Variant names:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_014783.6(ARHGAP11A):āc.359T>Gā(p.Leu120Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 30)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
ARHGAP11A
NM_014783.6 missense
NM_014783.6 missense
Scores
11
5
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.57
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.97
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ARHGAP11A | ENST00000361627.8 | c.359T>G | p.Leu120Arg | missense_variant | Exon 4 of 12 | 1 | NM_014783.6 | ENSP00000355090.3 | ||
| ARHGAP11A-SCG5 | ENST00000692248.1 | c.359T>G | p.Leu120Arg | missense_variant | Exon 4 of 14 | ENSP00000510771.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461514Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727046
GnomAD4 exome
AF:
AC:
1
AN:
1461514
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
727046
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
30
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;H;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Gain of methylation at L120 (P = 0.0283);Gain of methylation at L120 (P = 0.0283);Gain of methylation at L120 (P = 0.0283);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.