rs863225063

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_004815.4(ARHGAP29):​c.976A>T​(p.Lys326Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

ARHGAP29
NM_004815.4 stop_gained

Scores

5
1
1

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.74
Variant links:
Genes affected
ARHGAP29 (HGNC:30207): (Rho GTPase activating protein 29) Rap1 is a small GTPase that, through effectors, regulates Rho GTPase signaling. These effectors- Rasip1, Radil, and the protein encoded by this gene- translocate to the cell membrane, where they form a multiprotein complex. This complex is necessary for Rap1-induced inhibition of Rho signaling. Defects in this gene may be a cause of nonsyndromic cleft lip with or without cleft palate. [provided by RefSeq, Jun 2016]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARHGAP29NM_004815.4 linkuse as main transcriptc.976A>T p.Lys326Ter stop_gained 11/23 ENST00000260526.11 NP_004806.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARHGAP29ENST00000260526.11 linkuse as main transcriptc.976A>T p.Lys326Ter stop_gained 11/231 NM_004815.4 ENSP00000260526 P1Q52LW3-1
ARHGAP29ENST00000370217.3 linkuse as main transcriptc.976A>T p.Lys326Ter stop_gained 11/111 ENSP00000359237 Q52LW3-2
ARHGAP29ENST00000552844.5 linkuse as main transcriptc.976A>T p.Lys326Ter stop_gained, NMD_transcript_variant 11/261 ENSP00000449764

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, no assertion criteria providedliterature onlyOMIMNov 01, 2012- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.62
CADD
Pathogenic
37
DANN
Uncertain
1.0
Eigen
Pathogenic
0.91
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Pathogenic
0.98
D
MutationTaster
Benign
1.0
A;D
Vest4
0.39
GERP RS
6.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs863225063; hg19: chr1-94668267; API