14-102376774-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014844.5(TECPR2):āc.53A>Gā(p.Tyr18Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,614,176 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 Uncertain significance (ā ā ).
Frequency
Consequence
NM_014844.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TECPR2 | NM_014844.5 | c.53A>G | p.Tyr18Cys | missense_variant | Exon 2 of 20 | ENST00000359520.12 | NP_055659.2 | |
TECPR2 | NM_001172631.3 | c.53A>G | p.Tyr18Cys | missense_variant | Exon 2 of 17 | NP_001166102.1 | ||
LOC124903389 | XR_007064350.1 | n.73-6289T>C | intron_variant | Intron 1 of 2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TECPR2 | ENST00000359520.12 | c.53A>G | p.Tyr18Cys | missense_variant | Exon 2 of 20 | 1 | NM_014844.5 | ENSP00000352510.7 | ||
TECPR2 | ENST00000558678.1 | c.53A>G | p.Tyr18Cys | missense_variant | Exon 2 of 17 | 1 | ENSP00000453671.1 | |||
TECPR2 | ENST00000561228.1 | n.181A>G | non_coding_transcript_exon_variant | Exon 2 of 6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251468Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135912
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727248
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74462
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 49 Uncertain:2
This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 18 of the TECPR2 protein (p.Tyr18Cys). This variant is present in population databases (rs150645913, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TECPR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 408913). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. -
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Inborn genetic diseases Uncertain:1
The c.53A>G (p.Y18C) alteration is located in exon 2 (coding exon 1) of the TECPR2 gene. This alteration results from a A to G substitution at nucleotide position 53, causing the tyrosine (Y) at amino acid position 18 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Intellectual disability, FRA12A type Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at