rs73893124

Variant names:

• chr22-50068589-C-T
• rs73893124
• NM_015166.4:c.772-34G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-50068589-C-T
• chr22-50068589-C-A
• chr22-50068589-C-G

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.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 NM_015166.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.637
• Publications: 3 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=-0.9).
• BP6: Variant 22-50068589-C-T is Benign according to our data. Variant chr22-50068589-C-T is described in ClinVar as Benign. ClinVar VariationId 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.

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.772-34G>A		intron	N/A	NP_055981.1	Q15049-1
	MLC1	NM_001376472.1		c.772-34G>A		intron	N/A	NP_001363401.1	Q15049-1
	MLC1	NM_001376473.1		c.772-34G>A		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.772-34G>A		intron	N/A	ENSP00000310375.6	Q15049-1
	MLC1	ENST00000395876.6	TSL:1	c.772-34G>A		intron	N/A	ENSP00000379216.2	Q15049-1
	MLC1	ENST00000879262.1		c.772-34G>A		intron	N/A	ENSP00000549321.1

Frequencies

GnomAD3 genomes AF: 0.0675 AC: 9326 AN: 138100 Hom.: 978 Cov.: 31

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

GnomAD2 exomes AF: 0.0165 AC: 4098 AN: 248870 AF XY: 0.0123

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 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.: 35 AF XY: 0.00599 AC XY: 3643 AN XY: 608304

African (AFR) AF: 0.239 AC: 6763 AN: 28342

American (AMR) AF: 0.0126 AC: 480 AN: 38092

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 235 AN: 17258

East Asian (EAS) AF: 0.000110 AC: 2 AN: 18182

South Asian (SAS) AF: 0.000311 AC: 26 AN: 83546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32664

Middle Eastern (MID) AF: 0.00760 AC: 32 AN: 4210

European-Non Finnish (NFE) AF: 0.000322 AC: 309 AN: 959540

Other (OTH) AF: 0.0157 AC: 709 AN: 45256

GnomAD4 genome AF: 0.0676 AC: 9340 AN: 138208 Hom.: 978 Cov.: 31 AF XY: 0.0663 AC XY: 4417 AN XY: 66634

African (AFR) AF: 0.229 AC: 8825 AN: 38468

American (AMR) AF: 0.0250 AC: 345 AN: 13808

Ashkenazi Jewish (ASJ) AF: 0.00972 AC: 32 AN: 3292

East Asian (EAS) AF: 0.00 AC: 0 AN: 3906

South Asian (SAS) AF: 0.000512 AC: 2 AN: 3906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7746

Middle Eastern (MID) AF: 0.0108 AC: 3 AN: 278

European-Non Finnish (NFE) AF: 0.000656 AC: 42 AN: 63982

Other (OTH) AF: 0.0463 AC: 91 AN: 1964

Alfa AF: 0.00579 Hom.: 8

Bravo AF: 0.0710

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.81
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73893124; hg19: chr22-50507018;