rs1030933

chr1-84941966-A-Gchr1-84941966-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153259.4(MCOLN2):c.848-975T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,010 control chromosomes in the GnomAD database, including 24,350 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 0.56 (24350 hom., cov: 31)
• Consequence: MCOLN2 NM_153259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.42

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCOLN2	NM_153259.4	c.848-975T>C		intron_variant		ENST00000370608.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCOLN2	ENST00000370608.8	c.848-975T>C		intron_variant		1	NM_153259.4
MCOLN2	ENST00000531325.5	n.1089-975T>C		intron_variant, non_coding_transcript_variant		1
MCOLN2	ENST00000284027.5	c.764-975T>C		intron_variant		5		P1
MCOLN2	ENST00000463065.5	c.*45-3884T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85329 AN: 151892 Hom.: 24331 Cov.: 31

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.562 AC: 85394 AN: 152010 Hom.: 24350 Cov.: 31 AF XY: 0.567 AC XY: 42153 AN XY: 74286

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.525

Alfa AF: 0.550 Hom.: 7577

Bravo AF: 0.549

Asia WGS AF: 0.637 AC: 2216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.050
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1030933; hg19: chr1-85407649;