Variant rs6010165 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015166.4(MLC1):c.594C>T(p.Tyr198=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,612,906 control chromosomes in the GnomAD database, including 13,860 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1077 hom., cov: 33)

Exomes 𝑓: 0.13 ( 12783 hom. )

Consequence

MLC1
NM_015166.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.110

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:

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=-0.68).

BP6

Variant 22-50076844-G-A is Benign according to our data. Variant chr22-50076844-G-A is described in ClinVar as [Benign]. Clinvar id is 129614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLC1	NM_015166.4 linkuse as main transcript	c.594C>T	p.Tyr198=	synonymous_variant	7/12	ENST00000311597.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLC1	ENST00000311597.10 linkuse as main transcript	c.594C>T	p.Tyr198=	synonymous_variant	7/12	1	NM_015166.4	P1	Q15049-1
MLC1	ENST00000395876.6 linkuse as main transcript	c.594C>T	p.Tyr198=	synonymous_variant	7/12	1		P1	Q15049-1
MLC1	ENST00000442311.1 linkuse as main transcript	c.504C>T	p.Tyr168=	synonymous_variant	6/8	5

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17631

AN:

152086

Hom.:

1073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.0597

Gnomad EAS

AF:

0.0891

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.0724

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.131

GnomAD3 exomes

AF:

0.124

AC:

31262

AN:

251116

Hom.:

2155

AF XY:

0.131

AC XY:

17723

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.0669

Gnomad EAS exome

AF:

0.0878

Gnomad SAS exome

AF:

0.222

Gnomad FIN exome

AF:

0.0801

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.129

AC:

187899

AN:

1460702

Hom.:

12783

Cov.:

AF XY:

0.132

AC XY:

95684

AN XY:

726718

show subpopulations

Gnomad4 AFR exome

AF:

0.102

Gnomad4 AMR exome

AF:

0.130

Gnomad4 ASJ exome

AF:

0.0639

Gnomad4 EAS exome

AF:

0.0988

Gnomad4 SAS exome

AF:

0.222

Gnomad4 FIN exome

AF:

0.0842

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.116

AC:

17648

AN:

152204

Hom.:

1077

Cov.:

AF XY:

0.116

AC XY:

8648

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.157

Gnomad4 ASJ

AF:

0.0597

Gnomad4 EAS

AF:

0.0893

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.0724

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.119

Hom.:

1482

Bravo

AF:

0.119

Asia WGS

AF:

0.147

AC:

510

AN:

3478

EpiCase

AF:

0.117

EpiControl

AF:

0.123

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 10, 2021	- -
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. -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Megalencephalic leukoencephalopathy with subcortical cysts 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 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.

Dec 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.54

DANN

Benign

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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