rs12129308

chr1-84958037-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.411+492A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,180 control chromosomes in the GnomAD database, including 6,505 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 0.28 (6505 hom., cov: 32)
• Consequence: MCOLN2 NM_153259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCOLN2	NM_153259.4	c.411+492A>G		intron_variant		ENST00000370608.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCOLN2	ENST00000370608.8	c.411+492A>G		intron_variant		1	NM_153259.4
MCOLN2	ENST00000531325.5	n.652+492A>G		intron_variant, non_coding_transcript_variant		1
MCOLN2	ENST00000284027.5	c.327+492A>G		intron_variant		5		P1
MCOLN2	ENST00000463065.5	c.411+492A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42818 AN: 152062 Hom.: 6504 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.281 AC: 42832 AN: 152180 Hom.: 6505 Cov.: 32 AF XY: 0.279 AC XY: 20751 AN XY: 74392

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.273

Alfa AF: 0.309 Hom.: 1280

Bravo AF: 0.277

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.3
Dann	Benign	0.87

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: rs12129308; hg19: chr1-85423720;