X-22168313-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM5BP6BS2_Supporting
The NM_000444.6(PHEX):c.1406C>T(p.Ala469Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000822 in 1,179,772 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 30 hemizygotes in GnomAD. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A469E) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000444.6 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000108 AC: 12AN: 111611Hom.: 0 Cov.: 23 AF XY: 0.0000591 AC XY: 2AN XY: 33833
GnomAD3 exomes AF: 0.000158 AC: 29AN: 183147Hom.: 0 AF XY: 0.000103 AC XY: 7AN XY: 67749
GnomAD4 exome AF: 0.0000796 AC: 85AN: 1068161Hom.: 0 Cov.: 26 AF XY: 0.0000825 AC XY: 28AN XY: 339545
GnomAD4 genome AF: 0.000108 AC: 12AN: 111611Hom.: 0 Cov.: 23 AF XY: 0.0000591 AC XY: 2AN XY: 33833
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1406C>T (p.A469V) alteration is located in exon 13 (coding exon 13) of the PHEX gene. This alteration results from a C to T substitution at nucleotide position 1406, causing the alanine (A) at amino acid position 469 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at