rs561265847
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018368.4(LMBRD1):āc.1214C>Gā(p.Thr405Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,611,698 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. T405T) has been classified as Likely benign.
Frequency
Consequence
NM_018368.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LMBRD1 | NM_018368.4 | c.1214C>G | p.Thr405Ser | missense_variant | 13/16 | ENST00000649934.3 | |
LMBRD1 | NM_001363722.2 | c.995C>G | p.Thr332Ser | missense_variant | 13/16 | ||
LMBRD1 | NM_001367271.1 | c.995C>G | p.Thr332Ser | missense_variant | 13/16 | ||
LMBRD1 | NM_001367272.1 | c.995C>G | p.Thr332Ser | missense_variant | 13/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LMBRD1 | ENST00000649934.3 | c.1214C>G | p.Thr405Ser | missense_variant | 13/16 | NM_018368.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151674Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000797 AC: 20AN: 251006Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135680
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1459906Hom.: 1 Cov.: 30 AF XY: 0.0000220 AC XY: 16AN XY: 726328
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151792Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74202
ClinVar
Submissions by phenotype
Methylmalonic aciduria and homocystinuria type cblF Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 17, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 405 of the LMBRD1 protein (p.Thr405Ser). This variant is present in population databases (rs561265847, gnomAD 0.04%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with LMBRD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 580738). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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 | Jan 04, 2024 | The c.1214C>G (p.T405S) alteration is located in exon 13 (coding exon 13) of the LMBRD1 gene. This alteration results from a C to G substitution at nucleotide position 1214, causing the threonine (T) at amino acid position 405 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at