chr17-8318795-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_173728.4(ARHGEF15):c.1918G>C(p.Glu640Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,472 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E640K) has been classified as Uncertain significance.
Frequency
Consequence
NM_173728.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF15 | NM_173728.4 | c.1918G>C | p.Glu640Gln | missense_variant | 12/16 | ENST00000361926.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF15 | ENST00000361926.8 | c.1918G>C | p.Glu640Gln | missense_variant | 12/16 | 1 | NM_173728.4 | P1 | |
ARHGEF15 | ENST00000421050.2 | c.1918G>C | p.Glu640Gln | missense_variant | 12/16 | 1 | P1 | ||
ARHGEF15 | ENST00000647883.1 | c.1381G>C | p.Glu461Gln | missense_variant | 9/13 | ||||
ARHGEF15 | ENST00000582060.1 | n.30G>C | non_coding_transcript_exon_variant | 1/2 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 249994Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135472
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461280Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 726974
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74360
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 26, 2023 | The c.1918G>C (p.E640Q) alteration is located in exon 12 (coding exon 11) of the ARHGEF15 gene. This alteration results from a G to C substitution at nucleotide position 1918, causing the glutamic acid (E) at amino acid position 640 to be replaced by a glutamine (Q). 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