1-84985043-C-T

Position:

• chr1-84985043-C-T

Variant summary

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

The NM_153259.4(MCOLN2):​c.77+11753G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,684 control chromosomes in the GnomAD database, including 18,864 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 0.50 (18864 hom., cov: 29)
• Consequence: MCOLN2 NM_153259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453

Genes affected

MCOLN2 (HGNC:13357): (mucolipin TRP cation channel 2) Mucolipins constitute a family of cation channel proteins with homology to the transient receptor potential superfamily. In mammals, the mucolipin family includes 3 members, MCOLN1 (MIM 605248), MCOLN2, and MCOLN3 (MIM 607400), that exhibit a common 6-membrane-spanning topology. Homologs of mammalian mucolipins exist in Drosophila and C. elegans. Mutations in the human MCOLN1 gene cause mucolipodosis IV (MIM 262650) (Karacsonyi et al., 2007 [PubMed 17662026]).[supplied by OMIM, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCOLN2	NM_153259.4	c.77+11753G>A		intron_variant		ENST00000370608.8	NP_694991.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCOLN2	ENST00000370608.8	c.77+11753G>A		intron_variant		1	NM_153259.4	ENSP00000359640

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75063 AN: 151564 Hom.: 18860 Cov.: 29

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.495 AC: 75100 AN: 151684 Hom.: 18864 Cov.: 29 AF XY: 0.495 AC XY: 36686 AN XY: 74094

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.503

Alfa AF: 0.493 Hom.: 3126

Bravo AF: 0.489

Asia WGS AF: 0.413 AC: 1438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.79

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: rs10873672; hg19: chr1-85450726;