rs597630

Positions:

• chr1-84954264-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.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

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCOLN2	NM_153259.4	c.566-1734A>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.566-1734A>G		intron_variant		1	NM_153259.4	ENSP00000359640
MCOLN2	ENST00000531325.5	n.807-1734A>G		intron_variant, non_coding_transcript_variant		1
MCOLN2	ENST00000284027.5	c.482-1734A>G		intron_variant		5		ENSP00000284027	P1
MCOLN2	ENST00000463065.5	c.566-1734A>G		intron_variant, NMD_transcript_variant		2		ENSP00000436299

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

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.333

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.60
DANN	Benign	0.40

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: rs597630; hg19: chr1-85419947;