NM_020533.3:c.6A>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: G2P, ClinGen, Genomics England PanelApp, Ambry Genetics, Myriad Women’s Health, Orphanet, Labcorp Genetics (formerly Invitae)
• 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 VariationId is 1093444.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.11 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020533.3. 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
	MCOLN1	NM_020533.3	MANE Select	c.6A>G	p.Thr2Thr	synonymous	Exon 1 of 14	NP_065394.1	Q9GZU1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCOLN1	ENST00000264079.11	TSL:1 MANE Select	c.6A>G	p.Thr2Thr	synonymous	Exon 1 of 14	ENSP00000264079.5	Q9GZU1
	MCOLN1	ENST00000596390.1	TSL:1	n.122A>G		non_coding_transcript_exon	Exon 1 of 2
	MCOLN1	ENST00000852002.1		c.6A>G	p.Thr2Thr	synonymous	Exon 1 of 14	ENSP00000522061.1

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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Mucolipidosis type IV (1)

Computational scores

Source: dbNSFP v4.9

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;