chr1-204230478-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014935.5(PLEKHA6):c.2518C>T(p.Arg840Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,582,100 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. R840Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_014935.5 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 |
---|---|---|---|---|---|---|---|
PLEKHA6 | NM_014935.5 | c.2518C>T | p.Arg840Trp | missense_variant | 18/23 | ENST00000272203.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHA6 | ENST00000272203.8 | c.2518C>T | p.Arg840Trp | missense_variant | 18/23 | 1 | NM_014935.5 | P2 | |
PLEKHA6 | ENST00000637508.1 | c.2890C>T | p.Arg964Trp | missense_variant | 22/27 | 5 | A2 | ||
PLEKHA6 | ENST00000414478.1 | c.2578C>T | p.Arg860Trp | missense_variant | 18/23 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152242Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000256 AC: 5AN: 195502Hom.: 0 AF XY: 0.00000958 AC XY: 1AN XY: 104432
GnomAD4 exome AF: 0.0000308 AC: 44AN: 1429858Hom.: 0 Cov.: 31 AF XY: 0.0000297 AC XY: 21AN XY: 707824
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74378
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 26, 2022 | The c.2518C>T (p.R840W) alteration is located in exon 18 (coding exon 16) of the PLEKHA6 gene. This alteration results from a C to T substitution at nucleotide position 2518, causing the arginine (R) at amino acid position 840 to be replaced by a tryptophan (W). 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