rs536609

Variant names:

• chr1-84965168-T-C
• rs536609
• NM_153259.4:c.237+381A>G

Variant summary

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

The NM_153259.4(MCOLN2):​c.237+381A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,124 control chromosomes in the GnomAD database, including 9,920 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 (9920 hom., cov: 32)
• Consequence: MCOLN2 NM_153259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153259.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCOLN2	NM_153259.4	MANE Select	c.237+381A>G		intron	N/A	NP_694991.2
	MCOLN2	NM_001330647.2		c.153+381A>G		intron	N/A	NP_001317576.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCOLN2	ENST00000370608.8	TSL:1 MANE Select	c.237+381A>G		intron	N/A	ENSP00000359640.3
	MCOLN2	ENST00000531325.5	TSL:1	n.478+381A>G		intron	N/A
	MCOLN2	ENST00000284027.5	TSL:5	c.153+381A>G		intron	N/A	ENSP00000284027.5

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53779 AN: 152006 Hom.: 9901 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.354 AC: 53838 AN: 152124 Hom.: 9920 Cov.: 32 AF XY: 0.350 AC XY: 26018 AN XY: 74368

African (AFR) AF: 0.435 AC: 18042 AN: 41508

American (AMR) AF: 0.295 AC: 4501 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 963 AN: 3470

East Asian (EAS) AF: 0.381 AC: 1975 AN: 5180

South Asian (SAS) AF: 0.323 AC: 1556 AN: 4816

European-Finnish (FIN) AF: 0.243 AC: 2573 AN: 10588

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23259 AN: 67978

Other (OTH) AF: 0.331 AC: 699 AN: 2110

Alfa AF: 0.349 Hom.: 1595

Bravo AF: 0.358

Asia WGS AF: 0.352 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.79
DANN	Benign	0.39
PhyloP100		-0.74
Mutation Taster		=100/0	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: rs536609; hg19: chr1-85430851;