1-84960477-G-T

Variant names:

• chr1-84960477-G-T
• rs600924
• NM_153259.4:c.238-1775C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153259.4(MCOLN2):​c.238-1775C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 152,040 control chromosomes in the GnomAD database, including 9,612 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 0.35 (9612 hom., cov: 33)
• Consequence: MCOLN2 NM_153259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCOLN2	NM_153259.4	c.238-1775C>A		intron_variant	Intron 2 of 13	ENST00000370608.8	NP_694991.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCOLN2	ENST00000370608.8	c.238-1775C>A		intron_variant	Intron 2 of 13	1	NM_153259.4	ENSP00000359640.3
MCOLN2	ENST00000531325.5	n.479-1775C>A		intron_variant	Intron 2 of 11	1
MCOLN2	ENST00000284027.5	c.154-1775C>A		intron_variant	Intron 2 of 13	5		ENSP00000284027.5
MCOLN2	ENST00000463065.5	n.238-1775C>A		intron_variant	Intron 2 of 11	2		ENSP00000436299.1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53093 AN: 151920 Hom.: 9596 Cov.: 33

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.350 AC: 53150 AN: 152040 Hom.: 9612 Cov.: 33 AF XY: 0.346 AC XY: 25690 AN XY: 74322

African (AFR) AF: 0.419 AC: 17357 AN: 41442

American (AMR) AF: 0.294 AC: 4487 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 962 AN: 3468

East Asian (EAS) AF: 0.383 AC: 1981 AN: 5170

South Asian (SAS) AF: 0.323 AC: 1556 AN: 4820

European-Finnish (FIN) AF: 0.243 AC: 2571 AN: 10578

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.342 AC: 23268 AN: 67964

Other (OTH) AF: 0.330 AC: 698 AN: 2114

Alfa AF: 0.256 Hom.: 868

Bravo AF: 0.353

Asia WGS AF: 0.350 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.26
DANN	Benign	0.60
PhyloP100		-1.4
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs600924; hg19: chr1-85426160;