chr22-50084988-G-A

Position:

• chr22-50084988-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001376472.1(MLC1):​c.-86C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 1,569,394 control chromosomes in the GnomAD database, including 7,644 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.075 (503 hom., cov: 33)
  • Exomes 𝑓: 0.097 (7141 hom.)
• Consequence: MLC1 NM_001376472.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLC1	NM_015166.4	c.-59-27C>T		intron_variant		ENST00000311597.10	NP_055981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLC1	ENST00000311597.10	c.-59-27C>T		intron_variant		1	NM_015166.4	ENSP00000310375.6
MLC1	ENST00000395876.6	c.-59-27C>T		intron_variant		1		ENSP00000379216.2
MLC1	ENST00000442311.1	c.-59-27C>T		intron_variant		5		ENSP00000401385.1

Frequencies

GnomAD3 genomes AF: 0.0749 AC: 11404 AN: 152186 Hom.: 504 Cov.: 33

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0839

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.0696

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0907

Gnomad OTH AF: 0.0965

GnomAD4 exome AF: 0.0970 AC: 137523 AN: 1417090 Hom.: 7141 Cov.: 31 AF XY: 0.0996 AC XY: 70017 AN XY: 703048

Gnomad4 AFR exome AF: 0.0423

Gnomad4 AMR exome AF: 0.0718

Gnomad4 ASJ exome AF: 0.0476

Gnomad4 EAS exome AF: 0.0806

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.0723

Gnomad4 NFE exome AF: 0.0969

Gnomad4 OTH exome AF: 0.0959

GnomAD4 genome AF: 0.0749 AC: 11407 AN: 152304 Hom.: 503 Cov.: 33 AF XY: 0.0754 AC XY: 5615 AN XY: 74468

Gnomad4 AFR AF: 0.0407

Gnomad4 AMR AF: 0.0837

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.0698

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.0907

Gnomad4 OTH AF: 0.0964

Alfa AF: 0.0394 Hom.: 48

Bravo AF: 0.0744

Asia WGS AF: 0.105 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.48
DANN	Benign	0.59
BranchPoint Hunter		1.0

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: rs11568171; hg19: chr22-50523417;