chr1-84965168-T-C

Position:

• chr1-84965168-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.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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCOLN2	NM_153259.4	c.237+381A>G		intron_variant		ENST00000370608.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCOLN2	ENST00000370608.8	c.237+381A>G		intron_variant		1	NM_153259.4
MCOLN2	ENST00000531325.5	n.478+381A>G		intron_variant, non_coding_transcript_variant		1
MCOLN2	ENST00000284027.5	c.153+381A>G		intron_variant		5		P1
MCOLN2	ENST00000463065.5	c.237+381A>G		intron_variant, NMD_transcript_variant		2

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

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.331

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.79
DANN	Benign	0.39

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: rs536609; hg19: chr1-85430851;