rs79301

Variant names:

• chr22-50080294-A-G
• rs79301
• NM_015166.4:c.321+50T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-50080294-A-G
• chr22-50080294-A-C
• chr22-50080294-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015166.4(MLC1):​c.321+50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.933 in 1,562,152 control chromosomes in the GnomAD database, including 680,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68863 hom., cov: 33)
  • Exomes 𝑓: 0.93 (611747 hom.)
• Consequence: MLC1 NM_015166.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.59
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• megalencephalic leukoencephalopathy with subcortical cysts 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Myriad Women’s Health, G2P, Ambry Genetics
• megalencephalic leukoencephalopathy with subcortical cysts

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 22-50080294-A-G is Benign according to our data. Variant chr22-50080294-A-G is described in ClinVar as Benign. ClinVar VariationId is 260573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015166.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLC1	NM_015166.4	MANE Select	c.321+50T>C		intron	N/A	NP_055981.1	Q15049-1
	MLC1	NM_001376472.1		c.321+50T>C		intron	N/A	NP_001363401.1	Q15049-1
	MLC1	NM_001376473.1		c.321+50T>C		intron	N/A	NP_001363402.1	Q15049-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLC1	ENST00000311597.10	TSL:1 MANE Select	c.321+50T>C		intron	N/A	ENSP00000310375.6	Q15049-1
	MLC1	ENST00000395876.6	TSL:1	c.321+50T>C		intron	N/A	ENSP00000379216.2	Q15049-1
	MLC1	ENST00000879262.1		c.321+50T>C		intron	N/A	ENSP00000549321.1

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144630 AN: 152220 Hom.: 68798 Cov.: 33

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.982

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.936

GnomAD2 exomes AF: 0.949 AC: 192215 AN: 202522 AF XY: 0.949

Gnomad AFR exome AF: 0.989

Gnomad AMR exome AF: 0.957

Gnomad ASJ exome AF: 0.899

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.973

Gnomad NFE exome AF: 0.924

Gnomad OTH exome AF: 0.931

GnomAD4 exome AF: 0.931 AC: 1312951 AN: 1409814 Hom.: 611747 Cov.: 29 AF XY: 0.932 AC XY: 652305 AN XY: 699760

African (AFR) AF: 0.989 AC: 31646 AN: 32006

American (AMR) AF: 0.955 AC: 38566 AN: 40366

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 22850 AN: 25436

East Asian (EAS) AF: 0.999 AC: 37510 AN: 37530

South Asian (SAS) AF: 0.982 AC: 79842 AN: 81320

European-Finnish (FIN) AF: 0.971 AC: 48505 AN: 49944

Middle Eastern (MID) AF: 0.925 AC: 5255 AN: 5684

European-Non Finnish (NFE) AF: 0.921 AC: 993917 AN: 1078930

Other (OTH) AF: 0.936 AC: 54860 AN: 58598

GnomAD4 genome AF: 0.950 AC: 144754 AN: 152338 Hom.: 68863 Cov.: 33 AF XY: 0.953 AC XY: 71021 AN XY: 74496

African (AFR) AF: 0.986 AC: 41010 AN: 41582

American (AMR) AF: 0.952 AC: 14578 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3159 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5177 AN: 5182

South Asian (SAS) AF: 0.982 AC: 4737 AN: 4824

European-Finnish (FIN) AF: 0.974 AC: 10353 AN: 10626

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.921 AC: 62646 AN: 68024

Other (OTH) AF: 0.937 AC: 1979 AN: 2112

Alfa AF: 0.930 Hom.: 12231

Bravo AF: 0.950

Asia WGS AF: 0.992 AC: 3449 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Megalencephalic leukoencephalopathy with subcortical cysts 1 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.51
DANN	Benign	0.39
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs79301; hg19: chr22-50518723;