rs1647534032

Variant names:

• chr1-84938028-C-G
• rs1647534032
• NM_153259.4:c.1165G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153259.4(MCOLN2):​c.1165G>C​(p.Val389Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MCOLN2 NM_153259.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCOLN2	NM_153259.4	MANE Select	c.1165G>C	p.Val389Leu	missense	Exon 10 of 14	NP_694991.2
	MCOLN2	NM_001330647.2		c.1081G>C	p.Val361Leu	missense	Exon 11 of 15	NP_001317576.1	Q8IZK6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCOLN2	ENST00000370608.8	TSL:1 MANE Select	c.1165G>C	p.Val389Leu	missense	Exon 10 of 14	ENSP00000359640.3	Q8IZK6-1
	MCOLN2	ENST00000531325.5	TSL:1	n.1406G>C		non_coding_transcript_exon	Exon 10 of 12
	MCOLN2	ENST00000945493.1		c.1165G>C	p.Val389Leu	missense	Exon 10 of 14	ENSP00000615552.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.81	P
Vest4		0.52
MutPred		0.61		Loss of catalytic residue at V389 (P = 0.1845)
MVP		0.80
MPC		0.31
ClinPred		0.99	D
GERP RS		6.1
Varity_R		0.59
gMVP		0.89
Mutation Taster		=62/38	polymorphism

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: rs1647534032; hg19: chr1-85403711; COSMIC: COSV99033505;