Variant chr22-50068589-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000311597.10(MLC1):c.772-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,365,298 control chromosomes in the GnomAD database, including 1,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 978 hom., cov: 31)

Exomes 𝑓: 0.0070 ( 796 hom. )

Consequence

MLC1
ENST00000311597.10 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.637

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 22-50068589-C-T is Benign according to our data. Variant chr22-50068589-C-T is described in ClinVar as [Benign]. Clinvar id is 262459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 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.772-34G>A		intron_variant		ENST00000311597.10	NP_055981.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
MLC1	ENST00000311597.10 linkuse as main transcript	c.772-34G>A	intron_variant	1	NM_015166.4	ENSP00000310375	P1	Q15049-1
MLC1	ENST00000395876.6 linkuse as main transcript	c.772-34G>A	intron_variant	1		ENSP00000379216	P1	Q15049-1
MLC1	ENST00000483836.1 linkuse as main transcript	n.129-34G>A	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0675

AC:

9326

AN:

138100

Hom.:

978

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0250

Gnomad ASJ

AF:

0.00972

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000768

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00993

Gnomad NFE

AF:

0.000656

Gnomad OTH

AF:

0.0467

GnomAD3 exomes

AF:

0.0165

AC:

4098

AN:

248870

Hom.:

407

AF XY:

0.0123

AC XY:

1654

AN XY:

135012

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000463

Gnomad OTH exome

AF:

0.00790

GnomAD4 exome

AF:

0.00697

AC:

8556

AN:

1227090

Hom.:

796

Cov.:

AF XY:

0.00599

AC XY:

3643

AN XY:

608304

show subpopulations

Gnomad4 AFR exome

AF:

0.239

Gnomad4 AMR exome

AF:

0.0126

Gnomad4 ASJ exome

AF:

0.0136

Gnomad4 EAS exome

AF:

0.000110

Gnomad4 SAS exome

AF:

0.000311

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000322

Gnomad4 OTH exome

AF:

0.0157

GnomAD4 genome

AF:

0.0676

AC:

9340

AN:

138208

Hom.:

978

Cov.:

AF XY:

0.0663

AC XY:

4417

AN XY:

66634

show subpopulations

Gnomad4 AFR

AF:

0.229

Gnomad4 AMR

AF:

0.0250

Gnomad4 ASJ

AF:

0.00972

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000512

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000656

Gnomad4 OTH

AF:

0.0463

Alfa

AF:

0.00579

Hom.:

Bravo

AF:

0.0710

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 22, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.1

DANN

Benign

0.81

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