rs1555967227

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The ENST00000311597.10(MLC1):​c.448del​(p.Leu150SerfsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Consequence

MLC1
ENST00000311597.10 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.87
Variant links:
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 Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 22-50077477-AG-A is Pathogenic according to our data. Variant chr22-50077477-AG-A is described in ClinVar as [Pathogenic]. Clinvar id is 556409.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MLC1NM_015166.4 linkuse as main transcriptc.448del p.Leu150SerfsTer11 frameshift_variant 6/12 ENST00000311597.10 NP_055981.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MLC1ENST00000311597.10 linkuse as main transcriptc.448del p.Leu150SerfsTer11 frameshift_variant 6/121 NM_015166.4 ENSP00000310375 P1Q15049-1
MLC1ENST00000395876.6 linkuse as main transcriptc.448del p.Leu150SerfsTer11 frameshift_variant 6/121 ENSP00000379216 P1Q15049-1
MLC1ENST00000442311.1 linkuse as main transcriptc.358del p.Leu120SerfsTer11 frameshift_variant 5/85 ENSP00000401385

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Megalencephalic leukoencephalopathy with subcortical cysts 1 Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingCounsylJan 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1555967227; hg19: chr22-50515906; API