22-50059601-G-GC

Position:

• chr22-50059601-G-GC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015166.4(MLC1):​c.*1981_*1982insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,308 control chromosomes in the GnomAD database, including 1,322 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1322 hom., cov: 31)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: MLC1 NM_015166.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.111

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 22-50059601-G-GC is Benign according to our data. Variant chr22-50059601-G-GC is described in ClinVar as [Likely_benign]. Clinvar id is 342074.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLC1	NM_015166.4	c.*1981_*1982insG		3_prime_UTR_variant	12/12	ENST00000311597.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLC1	ENST00000311597.10	c.*1981_*1982insG		3_prime_UTR_variant	12/12	1	NM_015166.4	P1
MLC1	ENST00000395876.6	c.*1981_*1982insG		3_prime_UTR_variant	12/12	1		P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18780 AN: 152042 Hom.: 1322 Cov.: 31

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.0815

Gnomad EAS AF: 0.0897

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.115 AC: 17 AN: 148 Hom.: 0 Cov.: 0 AF XY: 0.111 AC XY: 10 AN XY: 90

Gnomad4 EAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.123 AC: 18784 AN: 152160 Hom.: 1322 Cov.: 31 AF XY: 0.124 AC XY: 9223 AN XY: 74396

Gnomad4 AFR AF: 0.0748

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.0815

Gnomad4 EAS AF: 0.0899

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.0858

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.147

Bravo AF: 0.126

Asia WGS AF: 0.149 AC: 515 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Megalencephalic leukoencephalopathy with subcortical cysts Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs145385166; hg19: chr22-50498030;