chr19-7522756-A-G

Variant names:

• chr19-7522756-A-G
• rs2146019165
• NM_020533.3:c.6A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_020533.3(MCOLN1):​c.6A>G​(p.Thr2Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000156 in 1,281,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: MCOLN1 NM_020533.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-7522756-A-G is Benign according to our data. Variant chr19-7522756-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1093444.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.11 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCOLN1	NM_020533.3	c.6A>G	p.Thr2Thr	synonymous_variant	Exon 1 of 14	ENST00000264079.11	NP_065394.1
LOC105372261	XR_936293.3	n.936+86T>C		intron_variant	Intron 2 of 2
LOC105372261	XR_936294.3	n.936+86T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCOLN1	ENST00000264079.11	c.6A>G	p.Thr2Thr	synonymous_variant	Exon 1 of 14	1	NM_020533.3	ENSP00000264079.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000156 AC: 2 AN: 1281586 Hom.: 0 Cov.: 30 AF XY: 0.00000159 AC XY: 1 AN XY: 627284

African (AFR) AF: 0.00 AC: 0 AN: 26020

American (AMR) AF: 0.00 AC: 0 AN: 22314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21728

East Asian (EAS) AF: 0.00 AC: 0 AN: 28272

South Asian (SAS) AF: 0.0000151 AC: 1 AN: 66232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3862

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1029232

Other (OTH) AF: 0.0000188 AC: 1 AN: 53208

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mucolipidosis type IV Benign:1

Dec 02, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.0
DANN	Benign	0.47
PhyloP100		-1.1
PromoterAI		0.22	Neutral
Mutation Taster		=100/0	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: rs2146019165; hg19: chr19-7587642;