chr10-30313734-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_018109.4(MTPAP):c.1624A>G(p.Thr542Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,614,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_018109.4 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 |
---|---|---|---|---|---|---|---|
MTPAP | NM_018109.4 | c.1624A>G | p.Thr542Ala | missense_variant | 9/9 | ENST00000263063.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTPAP | ENST00000263063.9 | c.1624A>G | p.Thr542Ala | missense_variant | 9/9 | 1 | NM_018109.4 | P1 | |
MTPAP | ENST00000488290.5 | n.3379A>G | non_coding_transcript_exon_variant | 17/17 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251418Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135882
GnomAD4 exome AF: 0.0000581 AC: 85AN: 1461870Hom.: 0 Cov.: 31 AF XY: 0.0000564 AC XY: 41AN XY: 727240
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74370
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 03, 2023 | Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools predict that this variant is not damaging. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2022 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 542 of the MTPAP protein (p.Thr542Ala). This variant is present in population databases (rs756511637, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with MTPAP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine 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