rs759754956
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP2BP4_ModerateBP6BS1BS2
The NM_001083962.2(TCF4):c.1318G>A(p.Gly440Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,636 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001083962.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCF4 | NM_001083962.2 | c.1318G>A | p.Gly440Ser | missense_variant | 15/20 | ENST00000354452.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCF4 | ENST00000354452.8 | c.1318G>A | p.Gly440Ser | missense_variant | 15/20 | 5 | NM_001083962.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152044Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 250886Hom.: 0 AF XY: 0.0000664 AC XY: 9AN XY: 135620
GnomAD4 exome AF: 0.0000281 AC: 41AN: 1461474Hom.: 0 Cov.: 32 AF XY: 0.0000426 AC XY: 31AN XY: 727040
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152162Hom.: 1 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74402
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 01, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Pitt-Hopkins syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at