chr3-33114100-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006371.5(CRTAP):c.23C>T(p.Ala8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000381 in 1,471,002 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. A8A) has been classified as Likely benign.
Frequency
Consequence
NM_006371.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRTAP | NM_006371.5 | c.23C>T | p.Ala8Val | missense_variant | 1/7 | ENST00000320954.11 | |
CRTAP | NM_001393363.1 | c.23C>T | p.Ala8Val | missense_variant | 1/6 | ||
CRTAP | NM_001393364.1 | c.23C>T | p.Ala8Val | missense_variant | 1/6 | ||
CRTAP | NM_001393365.1 | c.23C>T | p.Ala8Val | missense_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRTAP | ENST00000320954.11 | c.23C>T | p.Ala8Val | missense_variant | 1/7 | 1 | NM_006371.5 | P1 | |
CRTAP | ENST00000449224.1 | c.23C>T | p.Ala8Val | missense_variant | 1/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152090Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000248 AC: 2AN: 80800Hom.: 0 AF XY: 0.0000213 AC XY: 1AN XY: 46918
GnomAD4 exome AF: 0.0000417 AC: 55AN: 1318912Hom.: 0 Cov.: 32 AF XY: 0.0000368 AC XY: 24AN XY: 651348
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152090Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74296
ClinVar
Submissions by phenotype
Osteogenesis imperfecta Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 01, 2018 | - - |
Osteogenesis imperfecta type 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 14, 2021 | This sequence change replaces alanine with valine at codon 8 of the CRTAP protein (p.Ala8Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with CRTAP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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