chr20-14326252-T-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_198391.3(FLRT3):c.1255A>T(p.Thr419Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000126 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T419T) has been classified as Benign.
Frequency
Consequence
NM_198391.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLRT3 | NM_198391.3 | c.1255A>T | p.Thr419Ser | missense_variant | 3/3 | ENST00000341420.5 | |
MACROD2 | NM_001351661.2 | c.272-167227T>A | intron_variant | ENST00000684519.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLRT3 | ENST00000341420.5 | c.1255A>T | p.Thr419Ser | missense_variant | 3/3 | 2 | NM_198391.3 | P1 | |
MACROD2 | ENST00000684519.1 | c.272-167227T>A | intron_variant | NM_001351661.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152102Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000108 AC: 27AN: 250450Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135308
GnomAD4 exome AF: 0.000129 AC: 188AN: 1461670Hom.: 0 Cov.: 34 AF XY: 0.000117 AC XY: 85AN XY: 727134
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74404
ClinVar
Submissions by phenotype
Hypogonadotropic hypogonadism 21 with or without anosmia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 29, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2022 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1029224). This variant has not been reported in the literature in individuals affected with FLRT3-related conditions. This variant is present in population databases (rs769008665, gnomAD 0.02%). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 419 of the FLRT3 protein (p.Thr419Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at