rs597630

Variant names:

• chr1-84954264-T-C
• rs597630
• NM_153259.4:c.566-1734A>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.566-1734A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,044 control chromosomes in the GnomAD database, including 10,049 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 0.36 (10049 hom., cov: 32)
• Consequence: MCOLN2 NM_153259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 8 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 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.566-1734A>G		intron	N/A	NP_694991.2
	MCOLN2	NM_001330647.2		c.482-1734A>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.566-1734A>G		intron	N/A	ENSP00000359640.3
	MCOLN2	ENST00000531325.5	TSL:1	n.807-1734A>G		intron	N/A
	MCOLN2	ENST00000284027.5	TSL:5	c.482-1734A>G		intron	N/A	ENSP00000284027.5

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54069 AN: 151924 Hom.: 10027 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.356 AC: 54133 AN: 152044 Hom.: 10049 Cov.: 32 AF XY: 0.352 AC XY: 26150 AN XY: 74338

African (AFR) AF: 0.442 AC: 18307 AN: 41450

American (AMR) AF: 0.295 AC: 4509 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 964 AN: 3468

East Asian (EAS) AF: 0.388 AC: 2009 AN: 5178

South Asian (SAS) AF: 0.323 AC: 1556 AN: 4824

European-Finnish (FIN) AF: 0.242 AC: 2560 AN: 10580

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

European-Non Finnish (NFE) AF: 0.342 AC: 23257 AN: 67948

Other (OTH) AF: 0.333 AC: 701 AN: 2108

Alfa AF: 0.350 Hom.: 1603

Bravo AF: 0.360

Asia WGS AF: 0.354 AC: 1231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.60
DANN	Benign	0.40
PhyloP100		-1.3
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: rs597630; hg19: chr1-85419947;