10-76036105-C-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001305581.2(LRMDA):c.229C>G(p.Leu77Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000173 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. L77L) has been classified as Likely benign.
Frequency
Consequence
NM_001305581.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRMDA | NM_001305581.2 | c.229C>G | p.Leu77Val | missense_variant | 3/7 | ENST00000611255.5 | |
LRMDA | NM_032024.5 | c.145C>G | p.Leu49Val | missense_variant | 2/6 | ||
LRMDA | NR_131178.2 | n.583C>G | non_coding_transcript_exon_variant | 4/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRMDA | ENST00000611255.5 | c.229C>G | p.Leu77Val | missense_variant | 3/7 | 5 | NM_001305581.2 | P1 | |
LRMDA | ENST00000372499.5 | c.145C>G | p.Leu49Val | missense_variant | 2/6 | 1 | |||
LRMDA | ENST00000593699.5 | n.583C>G | non_coding_transcript_exon_variant | 4/8 | 1 | ||||
LRMDA | ENST00000593817.1 | n.190C>G | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251368Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135850
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461798Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 727200
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74332
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 12, 2021 | The c.145C>G (p.L49V) alteration is located in exon 2 (coding exon 2) of the C10orf11 gene. This alteration results from a C to G substitution at nucleotide position 145, causing the leucine (L) at amino acid position 49 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 01, 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with C10orf11-related conditions. This variant is present in population databases (rs758722866, gnomAD 0.007%). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 49 of the C10orf11 protein (p.Leu49Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at