rs146011150
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001370658.1(BTD):c.68A>G(p.His23Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000634 in 1,614,048 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001370658.1 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 |
---|---|---|---|---|---|---|---|
BTD | NM_001370658.1 | c.68A>G | p.His23Arg | missense_variant | 2/4 | ENST00000643237.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BTD | ENST00000643237.3 | c.68A>G | p.His23Arg | missense_variant | 2/4 | NM_001370658.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000414 AC: 63AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000358 AC: 90AN: 251424Hom.: 1 AF XY: 0.000383 AC XY: 52AN XY: 135884
GnomAD4 exome AF: 0.000657 AC: 961AN: 1461892Hom.: 1 Cov.: 32 AF XY: 0.000635 AC XY: 462AN XY: 727246
GnomAD4 genome ? AF: 0.000414 AC: 63AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.000350 AC XY: 26AN XY: 74336
ClinVar
Submissions by phenotype
Biotinidase deficiency Uncertain:3Benign:1Other:1
Likely benign, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Jan 01, 2019 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 04, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 22, 2022 | - - |
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 43 of the BTD protein (p.His43Arg). This variant is present in population databases (rs146011150, gnomAD 0.07%). This missense change has been observed in individual(s) with a positive newborn screening result for BTD-related disease (PMID: 26810761). ClinVar contains an entry for this variant (Variation ID: 38483). 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 arginine 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2022 | The c.128A>G (p.H43R) alteration is located in exon 2 (coding exon 2) of the BTD gene. This alteration results from a A to G substitution at nucleotide position 128, causing the histidine (H) at amino acid position 43 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Intellectual disability Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille | Jan 01, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at