22-50064163-TAGC-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3
The NM_015166.4(MLC1):c.927_929delGCT(p.Leu310del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000525 in 1,600,600 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000055 ( 0 hom. )
Consequence
MLC1
NM_015166.4 disruptive_inframe_deletion
NM_015166.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.94
Genes affected
MLC1 (HGNC:17082): (modulator of VRAC current 1) The function of this gene product is unknown; however, homology to other proteins suggests that it may be an integral membrane transporter. Mutations in this gene have been associated with megalencephalic leukoencephalopathy with subcortical cysts, an autosomal recessive neurological disorder. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_015166.4
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MLC1 | NM_015166.4 | c.927_929delGCT | p.Leu310del | disruptive_inframe_deletion | 11/12 | ENST00000311597.10 | NP_055981.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MLC1 | ENST00000311597.10 | c.927_929delGCT | p.Leu310del | disruptive_inframe_deletion | 11/12 | 1 | NM_015166.4 | ENSP00000310375.6 | ||
MLC1 | ENST00000395876.6 | c.927_929delGCT | p.Leu310del | disruptive_inframe_deletion | 11/12 | 1 | ENSP00000379216.2 | |||
MLC1 | ENST00000483836.1 | n.284_286delGCT | non_coding_transcript_exon_variant | 4/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 151904Hom.: 0 Cov.: 34
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GnomAD4 exome AF: 0.0000545 AC: 79AN: 1448696Hom.: 0 AF XY: 0.0000596 AC XY: 43AN XY: 720970
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 151904Hom.: 0 Cov.: 34 AF XY: 0.0000404 AC XY: 3AN XY: 74192
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 09, 2022 | This variant, c.927_929del, results in the deletion of 1 amino acid(s) of the MLC1 protein (p.Leu310del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MLC1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
MLC1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 24, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at