rs746287594
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_001099274.3(TINF2):c.631C>G(p.Leu211Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,884 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. L211L) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TINF2 | NM_001099274.3 | c.631C>G | p.Leu211Val | missense_variant | 6/9 | ENST00000267415.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TINF2 | ENST00000267415.12 | c.631C>G | p.Leu211Val | missense_variant | 6/9 | 1 | NM_001099274.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000805 AC: 2AN: 248374Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 135008
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461744Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727156
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74316
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 15, 2016 | - - |
Dyskeratosis congenita Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 15, 2023 | 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine 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: 437006). This variant has not been reported in the literature in individuals affected with TINF2-related conditions. This variant is present in population databases (rs746287594, gnomAD 0.002%). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 211 of the TINF2 protein (p.Leu211Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at