chr1-84985237-T-C

Position:

• chr1-84985237-T-C

Variant summary

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

The NM_153259.4(MCOLN2):​c.77+11559A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,958 control chromosomes in the GnomAD database, including 15,183 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 0.44 (15183 hom., cov: 32)
• Consequence: MCOLN2 NM_153259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCOLN2	NM_153259.4	c.77+11559A>G		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+11559A>G		intron_variant		1	NM_153259.4	ENSP00000359640

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66238 AN: 151840 Hom.: 15187 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.436 AC: 66257 AN: 151958 Hom.: 15183 Cov.: 32 AF XY: 0.438 AC XY: 32509 AN XY: 74284

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.437

Alfa AF: 0.474 Hom.: 35324

Bravo AF: 0.435

Asia WGS AF: 0.544 AC: 1892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.8
DANN	Benign	0.59

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: rs6691970; hg19: chr1-85450920;