22-50064163-TAGCAGCAGC-TAGCAGCAGCAGCAGC
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3
The NM_015166.4(MLC1):c.924_929dupGCTGCT(p.Leu309_Leu310dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,610 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L310L) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
MLC1
NM_015166.4 disruptive_inframe_insertion
NM_015166.4 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.94
Publications
1 publications found
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]
MLC1 Gene-Disease associations (from GenCC):
- megalencephalic leukoencephalopathy with subcortical cysts 1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Myriad Women’s Health
- megalencephalic leukoencephalopathy with subcortical cystsInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 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 rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MLC1 | NM_015166.4 | c.924_929dupGCTGCT | p.Leu309_Leu310dup | disruptive_inframe_insertion | Exon 11 of 12 | ENST00000311597.10 | NP_055981.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| MLC1 | ENST00000311597.10 | c.924_929dupGCTGCT | p.Leu309_Leu310dup | disruptive_inframe_insertion | Exon 11 of 12 | 1 | NM_015166.4 | ENSP00000310375.6 | ||
| MLC1 | ENST00000395876.6 | c.924_929dupGCTGCT | p.Leu309_Leu310dup | disruptive_inframe_insertion | Exon 11 of 12 | 1 | ENSP00000379216.2 | |||
| MLC1 | ENST00000483836.1 | n.281_286dupGCTGCT | non_coding_transcript_exon_variant | Exon 4 of 5 | 2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
34
GnomAD2 exomes AF: 0.00000856 AC: 2AN: 233570 AF XY: 0.00000783 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
233570
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1452610Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0AN XY: 722836 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1452610
Hom.:
Cov.:
39
AF XY:
AC XY:
0
AN XY:
722836
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33420
American (AMR)
AF:
AC:
0
AN:
44586
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26040
East Asian (EAS)
AF:
AC:
0
AN:
39670
South Asian (SAS)
AF:
AC:
0
AN:
85904
European-Finnish (FIN)
AF:
AC:
0
AN:
46010
Middle Eastern (MID)
AF:
AC:
0
AN:
5700
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111064
Other (OTH)
AF:
AC:
0
AN:
60216
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
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2
0.00
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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10
<30
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
34
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Jul 22, 2021
AiLife Diagnostics, AiLife Diagnostics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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