20-38629547-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001164431.3(ARHGAP40):​c.680C>G​(p.Ala227Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A227D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ARHGAP40
NM_001164431.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.168
Variant links:
Genes affected
ARHGAP40 (HGNC:16226): (Rho GTPase activating protein 40) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of actin filament polymerization and regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.056130618).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARHGAP40NM_001164431.3 linkc.680C>G p.Ala227Gly missense_variant Exon 5 of 15 NP_001157903.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARHGAP40ENST00000373345.9 linkc.680C>G p.Ala227Gly missense_variant Exon 5 of 15 5 ENSP00000362442.5 Q5TG30
ARHGAP40ENST00000243967.8 linkc.341C>G p.Ala114Gly missense_variant Exon 3 of 14 5 ENSP00000243967.4 H7BXE0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.091
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
7.6
DANN
Benign
0.95
DEOGEN2
Benign
0.0070
T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.078
N
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.056
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.91
N
REVEL
Benign
0.017
Sift
Benign
0.33
T
Sift4G
Benign
0.34
T
Vest4
0.078
MutPred
0.13
Loss of stability (P = 0.0605);
MVP
0.092
ClinPred
0.062
T
GERP RS
1.7
Varity_R
0.053
gMVP
0.19

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs983848149; hg19: chr20-37258190; API