rs11568186

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015166.4(MLC1):c.978C>T(p.Cys326Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,506,278 control chromosomes in the GnomAD database, including 15,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1210 hom., cov: 33)

Exomes 𝑓: 0.12 ( 14778 hom. )

Consequence

MLC1
NM_015166.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.23

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 links:

MLC1 (HGNC:):

MLC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 22-50064115-G-A is Benign according to our data. Variant chr22-50064115-G-A is described in ClinVar as [Benign]. Clinvar id is 129617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLC1	NM_015166.4 linkuse as main transcript	c.978C>T	p.Cys326Cys	synonymous_variant	11/12	ENST00000311597.10	NP_055981.1	Q15049-1A0A024R4V4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MLC1	ENST00000311597.10 linkuse as main transcript	c.978C>T	p.Cys326Cys	synonymous_variant	11/12	1	NM_015166.4	ENSP00000310375.6	Q15049-1
MLC1	ENST00000395876.6 linkuse as main transcript	c.978C>T	p.Cys326Cys	synonymous_variant	11/12	1		ENSP00000379216.2	Q15049-1
MLC1	ENST00000483836.1 linkuse as main transcript	n.335C>T		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

16913

AN:

148738

Hom.:

1210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0682

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.0747

Gnomad EAS

AF:

0.0886

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.0780

Gnomad MID

AF:

0.100

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.140

GnomAD3 exomes

AF:

0.129

AC:

31409

AN:

243248

Hom.:

2325

AF XY:

0.136

AC XY:

17956

AN XY:

132104

show subpopulations

Gnomad AFR exome

AF:

0.0693

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.0835

Gnomad EAS exome

AF:

0.0921

Gnomad SAS exome

AF:

0.214

Gnomad FIN exome

AF:

0.0772

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.122

AC:

165321

AN:

1357424

Hom.:

14778

Cov.:

AF XY:

0.125

AC XY:

84293

AN XY:

675902

show subpopulations

Gnomad4 AFR exome

AF:

0.0588

Gnomad4 AMR exome

AF:

0.115

Gnomad4 ASJ exome

AF:

0.0712

Gnomad4 EAS exome

AF:

0.0901

Gnomad4 SAS exome

AF:

0.198

Gnomad4 FIN exome

AF:

0.0751

Gnomad4 NFE exome

AF:

0.123

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.114

AC:

16917

AN:

148854

Hom.:

1210

Cov.:

AF XY:

0.114

AC XY:

8298

AN XY:

72758

show subpopulations

Gnomad4 AFR

AF:

0.0684

Gnomad4 AMR

AF:

0.165

Gnomad4 ASJ

AF:

0.0747

Gnomad4 EAS

AF:

0.0889

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.0780

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.122

Hom.:

553

Bravo

AF:

0.124

Asia WGS

AF:

0.114

AC:

382

AN:

3370

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 20, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Megalencephalic leukoencephalopathy with subcortical cysts 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Megalencephalic leukoencephalopathy with subcortical cysts

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Nov 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

1.9

DANN

Benign

0.91

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over