rs11568190
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_015166.4(MLC1):c.1053T>G(p.Ala351Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000735 in 1,361,044 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A351A) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 33)
Exomes 𝑓: 7.3e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MLC1
NM_015166.4 synonymous
NM_015166.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -6.10
Publications
9 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: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.0).
BP6
Variant 22-50064040-A-C is Benign according to our data. Variant chr22-50064040-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2177841.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-6.1 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MLC1 | NM_015166.4 | c.1053T>G | p.Ala351Ala | synonymous_variant | 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.1053T>G | p.Ala351Ala | synonymous_variant | Exon 11 of 12 | 1 | NM_015166.4 | ENSP00000310375.6 | ||
| MLC1 | ENST00000395876.6 | c.1053T>G | p.Ala351Ala | synonymous_variant | Exon 11 of 12 | 1 | ENSP00000379216.2 | |||
| MLC1 | ENST00000483836.1 | n.410T>G | non_coding_transcript_exon_variant | Exon 4 of 5 | 2 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 137918Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
0
AN:
137918
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 7.35e-7 AC: 1AN: 1361044Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 677722 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1361044
Hom.:
Cov.:
36
AF XY:
AC XY:
0
AN XY:
677722
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
32510
American (AMR)
AF:
AC:
0
AN:
42442
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25424
East Asian (EAS)
AF:
AC:
0
AN:
38622
South Asian (SAS)
AF:
AC:
0
AN:
80868
European-Finnish (FIN)
AF:
AC:
0
AN:
43860
Middle Eastern (MID)
AF:
AC:
0
AN:
4686
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1035582
Other (OTH)
AF:
AC:
0
AN:
57050
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00 AC: 0AN: 138046Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 67404
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
138046
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
67404
African (AFR)
AF:
AC:
0
AN:
38634
American (AMR)
AF:
AC:
0
AN:
13618
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3284
East Asian (EAS)
AF:
AC:
0
AN:
4746
South Asian (SAS)
AF:
AC:
0
AN:
3928
European-Finnish (FIN)
AF:
AC:
0
AN:
9728
Middle Eastern (MID)
AF:
AC:
0
AN:
276
European-Non Finnish (NFE)
AF:
AC:
0
AN:
61144
Other (OTH)
AF:
AC:
0
AN:
1892
Alfa
AF:
Hom.:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Dec 20, 2021
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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