GeneBe

NM_015166.4:c.772-35C>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015166.4(MLC1):​c.772-35C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MLC1
NM_015166.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.44

Publications

7 publications found
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]
MLC1 Gene-Disease associations (from GenCC):
  • megalencephalic leukoencephalopathy with subcortical cysts 1
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Myriad Women’s Health
  • megalencephalic leukoencephalopathy with subcortical cysts
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MLC1NM_015166.4 linkc.772-35C>A intron_variant Intron 9 of 11 ENST00000311597.10 NP_055981.1 Q15049-1A0A024R4V4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MLC1ENST00000311597.10 linkc.772-35C>A intron_variant Intron 9 of 11 1 NM_015166.4 ENSP00000310375.6 Q15049-1
MLC1ENST00000395876.6 linkc.772-35C>A intron_variant Intron 9 of 11 1 ENSP00000379216.2 Q15049-1
MLC1ENST00000483836.1 linkn.129-35C>A intron_variant Intron 2 of 4 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1452910
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
722826
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33008
American (AMR)
AF:
0.00
AC:
0
AN:
44474
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25936
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39366
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85942
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51690
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5332
European-Non Finnish (NFE)
AF:
9.03e-7
AC:
1
AN:
1107390
Other (OTH)
AF:
0.00
AC:
0
AN:
59772
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.00
Hom.:
129

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.16
DANN
Benign
0.42
PhyloP100
-2.4

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

Other links and lift over

dbSNP: rs11568179; hg19: chr22-50507019; API