2-130946624-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001367493.1(ARHGEF4):c.3974C>A(p.Thr1325Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001367493.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARHGEF4 | NM_001367493.1 | c.3974C>A | p.Thr1325Lys | missense_variant | Exon 4 of 14 | ENST00000409359.7 | NP_001354422.1 | |
ARHGEF4 | NM_001375900.1 | c.461C>A | p.Thr154Lys | missense_variant | Exon 3 of 13 | NP_001362829.1 | ||
ARHGEF4 | NM_015320.4 | c.416C>A | p.Thr139Lys | missense_variant | Exon 5 of 15 | NP_056135.2 | ||
ARHGEF4 | NM_001375901.1 | c.305C>A | p.Thr102Lys | missense_variant | Exon 6 of 16 | NP_001362830.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152224Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251404Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135862
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461758Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 727170
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.416C>A (p.T139K) alteration is located in exon 4 (coding exon 2) of the ARHGEF4 gene. This alteration results from a C to A substitution at nucleotide position 416, causing the threonine (T) at amino acid position 139 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at