chr6-69676168-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_018368.4(LMBRD1):c.1613A>G(p.Tyr538Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,026 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 (★). Synonymous variant affecting the same amino acid position (i.e. Y538Y) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LMBRD1 | NM_018368.4 | c.1613A>G | p.Tyr538Cys | missense_variant | 16/16 | ENST00000649934.3 | |
LMBRD1 | NM_001363722.2 | c.1394A>G | p.Tyr465Cys | missense_variant | 16/16 | ||
LMBRD1 | NM_001367271.1 | c.1394A>G | p.Tyr465Cys | missense_variant | 16/16 | ||
LMBRD1 | NM_001367272.1 | c.1394A>G | p.Tyr465Cys | missense_variant | 16/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LMBRD1 | ENST00000649934.3 | c.1613A>G | p.Tyr538Cys | missense_variant | 16/16 | NM_018368.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250752Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135500
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460026Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4AN XY: 726374
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Methylmalonic aciduria and homocystinuria type cblF Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2022 | 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. 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1487617). This variant has not been reported in the literature in individuals affected with LMBRD1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 538 of the LMBRD1 protein (p.Tyr538Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at