rs2022509435

Variant names:

• chr19-7522649-T-C
• rs2022509435
• ENST00000596390.1:n.15T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-7522649-T-C
• chr19-7522649-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000596390.1(MCOLN1):​n.15T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000877 in 1,140,312 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: MCOLN1 ENST00000596390.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 0 publications found

Genes affected

MCOLN1 (HGNC:13356): (mucolipin TRP cation channel 1) This gene encodes a memberof the transient receptor potential (TRP) cation channel gene family. The transmembrane protein localizes to intracellular vesicular membranes including lysosomes, and functions in the late endocytic pathway and in the regulation of lysosomal exocytosis. The channel is permeable to Ca(2+), Fe(2+), Na(+), K(+), and H(+), and is modulated by changes in Ca(2+) concentration. Mutations in this gene result in mucolipidosis type IV. [provided by RefSeq, Oct 2009]

MCOLN1 Gene-Disease associations (from GenCC):

• mucolipidosis type IV

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, ClinGen, G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Lisch epithelial corneal dystrophy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000305089 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCOLN1	NM_020533.3	c.-102T>C		5_prime_UTR_variant	Exon 1 of 14	ENST00000264079.11	NP_065394.1
LOC105372261	XR_936293.3	n.936+193A>G		intron_variant	Intron 2 of 2
LOC105372261	XR_936294.3	n.936+193A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCOLN1	ENST00000264079.11	c.-102T>C		5_prime_UTR_variant	Exon 1 of 14	1	NM_020533.3	ENSP00000264079.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.77e-7 AC: 1 AN: 1140312 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 561822

African (AFR) AF: 0.00 AC: 0 AN: 23030

American (AMR) AF: 0.00 AC: 0 AN: 19990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19388

East Asian (EAS) AF: 0.0000362 AC: 1 AN: 27588

South Asian (SAS) AF: 0.00 AC: 0 AN: 60494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3466

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 907814

Other (OTH) AF: 0.00 AC: 0 AN: 48208

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Benign	0.91
PhyloP100		1.8
PromoterAI		-0.16	Neutral

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: rs2022509435; hg19: chr19-7587535;