chrX-71101176-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_005938.4(FOXO4):c.946C>T(p.His316Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000455 in 1,098,178 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 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. H316R) has been classified as Uncertain significance.
Frequency
Consequence
NM_005938.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 exomes AF: 0.00000551 AC: 1AN: 181366Hom.: 0 AF XY: 0.0000149 AC XY: 1AN XY: 67268
GnomAD4 exome AF: 0.0000455 AC: 50AN: 1098178Hom.: 0 Cov.: 32 AF XY: 0.0000303 AC XY: 11AN XY: 363534
GnomAD4 genome Cov.: 22
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.946C>T (p.H316Y) alteration is located in exon 2 (coding exon 2) of the FOXO4 gene. This alteration results from a C to T substitution at nucleotide position 946, causing the histidine (H) at amino acid position 316 to be replaced by a tyrosine (Y). 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