rs1555967644

Positions:

• chr22-50079809-GTGAATAACATTTACCACCTATTTCCAGCTCAACAAACATTTGCTGACACCATTCGTGGGAGTGGGGCTGTGGGTGTCAGGCGTCTGCGCGAAGCTCGTGTGAACTCACGTTTATTGCTGATGGGTTCAGGACTAGTTTGCATCCAAACCAAATTAAACACGTAGTGGTCACAGCAAACGTGGAAACAAACAATATCTGAAAGTTGGGAATCTGAAAAACAAGGCAGGAGGGGTTTTCCTTCTTTGAATAATAAAAGAAAAAAGGTAACAGATAAACCACACTTCAGGCCATTCACTAAAAATTATCCTGATTAGGACATAATGGTGGGGAGTCCTGCGTGCTCAGCCCGCTCTCCCCTCTGTGCGGCAAAGGCTGGGCTGGGCAGGAGCTTTACTGTCTGGGGGGCAACCTCGGGGGCCCCTCTCGGTGCCACAACGTCTGTGCGTGGGCACACACACAAGCACACATGGGCACACTGTCTGTCAGCCCCTCCGGCTTTCTCCCTGGCAGAGGCTGCCTGCAAGCTAGACTCACCACATTGGCGTTCCTCCTGGAGAC-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_015166.4(MLC1):​c.298_423+108del variant causes a splice acceptor, splice donor, splice donor 5th base, coding sequence, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MLC1 NM_015166.4 splice_acceptor, splice_donor, splice_donor_5th_base, coding_sequence, intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.186

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 Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.089065254 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLC1	NM_015166.4	c.298_423+108del		splice_acceptor_variant, splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	4/12	ENST00000311597.10	NP_055981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLC1	ENST00000311597.10	c.298_423+108del		splice_acceptor_variant, splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	4/12	1	NM_015166.4	ENSP00000310375	P1
MLC1	ENST00000395876.6	c.298_423+108del		splice_acceptor_variant, splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	4/12	1		ENSP00000379216	P1
MLC1	ENST00000442311.1	c.208_333+108del		splice_acceptor_variant, splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	3/8	5		ENSP00000401385

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Megalencephalic leukoencephalopathy with subcortical cysts 1 Other:1

not provided, no classification provided

literature only

GeneReviews

-

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555967644; hg19: chr22-50518238;