14-24239849-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001099274.3(TINF2):c.1304G>A(p.Gly435Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. G435G) has been classified as Likely benign.
Frequency
Consequence
NM_001099274.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TINF2 | NM_001099274.3 | c.1304G>A | p.Gly435Asp | missense_variant | 9/9 | ENST00000267415.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TINF2 | ENST00000267415.12 | c.1304G>A | p.Gly435Asp | missense_variant | 9/9 | 1 | NM_001099274.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249582Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135410
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727248
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152126Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74292
ClinVar
Submissions by phenotype
Dyskeratosis congenita Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 25, 2022 | This variant has not been reported in the literature in individuals affected with TINF2-related conditions. This variant is present in population databases (rs759420690, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 435 of the TINF2 protein (p.Gly435Asp). 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. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at