rs747138265
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_005249.5(FOXG1):c.1278G>A(p.Met426Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000273 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. M426V) has been classified as Uncertain significance.
Frequency
Consequence
NM_005249.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXG1 | NM_005249.5 | c.1278G>A | p.Met426Ile | missense_variant | 1/1 | ENST00000313071.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXG1 | ENST00000313071.7 | c.1278G>A | p.Met426Ile | missense_variant | 1/1 | NM_005249.5 | P1 | ||
FOXG1 | ENST00000706482.1 | c.1278G>A | p.Met426Ile | missense_variant | 2/2 | P1 | |||
LINC01551 | ENST00000675861.1 | n.374+2544G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251356Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135882
GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461872Hom.: 0 Cov.: 34 AF XY: 0.0000248 AC XY: 18AN XY: 727240
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74306
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 05, 2016 | - - |
Rett syndrome, congenital variant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 23, 2019 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FOXG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 205477). This variant is present in population databases (rs747138265, ExAC 0.002%). This sequence change replaces methionine with isoleucine at codon 426 of the FOXG1 protein (p.Met426Ile). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and isoleucine. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 24, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 20, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at