chr22-50060214-A-AT

Position:

• chr22-50060214-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_015166.4(MLC1):​c.*1368_*1369insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 152,354 control chromosomes in the GnomAD database, including 34 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (34 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MLC1 NM_015166.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.73

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 22-50060214-A-AT is Benign according to our data. Variant chr22-50060214-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 342082.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0127 (1942/152354) while in subpopulation EAS AF= 0.0411 (213/5186). AF 95% confidence interval is 0.0366. There are 34 homozygotes in gnomad4. There are 1156 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLC1	NM_015166.4	c.*1368_*1369insA		3_prime_UTR_variant	12/12	ENST00000311597.10	NP_055981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLC1	ENST00000311597.10	c.*1368_*1369insA		3_prime_UTR_variant	12/12	1	NM_015166.4	ENSP00000310375	P1
MLC1	ENST00000395876.6	c.*1368_*1369insA		3_prime_UTR_variant	12/12	1		ENSP00000379216	P1

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1943 AN: 152236 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.0412

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.0468

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00779

Gnomad OTH AF: 0.00716

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 154 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 84

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0127 AC: 1942 AN: 152354 Hom.: 34 Cov.: 33 AF XY: 0.0155 AC XY: 1156 AN XY: 74496

Gnomad4 AFR AF: 0.00233

Gnomad4 AMR AF: 0.0239

Gnomad4 ASJ AF: 0.00835

Gnomad4 EAS AF: 0.0411

Gnomad4 SAS AF: 0.0399

Gnomad4 FIN AF: 0.0468

Gnomad4 NFE AF: 0.00779

Gnomad4 OTH AF: 0.00709

Alfa AF: 0.0118 Hom.: 3

Bravo AF: 0.0106

Asia WGS AF: 0.0510 AC: 175 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: rs200990035; hg19: chr22-50498643;