MLC1 p.Ala351Ala

Variant names:

• chr22-50064039-C-C
• NM_015166.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr22-50064040--
• chr22-50064040-A-G
• chr22-50064040-A-T
• chr22-50064040-A-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015166.4(MLC1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MLC1 NM_015166.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.10
• Publications: 0 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: Myriad Women's Health, G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• megalencephalic leukoencephalopathy with subcortical cysts

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.		exon_region	Exon 11 of 12	NP_055981.1	Q15049-1
	MLC1	NM_001376472.1		c.		exon_region	Exon 10 of 11	NP_001363401.1	Q15049-1
	MLC1	NM_001376473.1		c.		exon_region	Exon 12 of 13	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.		exon_region	Exon 11 of 12	ENSP00000310375.6	Q15049-1
	MLC1	ENST00000395876.6	TSL:1	c.		exon_region	Exon 11 of 12	ENSP00000379216.2	Q15049-1
	MLC1	ENST00000879262.1		c.		exon_region	Exon 12 of 13	ENSP00000549321.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-6.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-50502468;