19-7522766-G-A

Variant names:

• chr19-7522766-G-A
• rs61736595
• NM_020533.3:c.16G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020533.3(MCOLN1):​c.16G>A​(p.Gly6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MCOLN1 NM_020533.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512

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]

LOC105372261 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28997543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCOLN1	NM_020533.3	c.16G>A	p.Gly6Ser	missense_variant	Exon 1 of 14	ENST00000264079.11	NP_065394.1
LOC105372261	XR_936293.3	n.936+76C>T		intron_variant	Intron 2 of 2
LOC105372261	XR_936294.3	n.936+76C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCOLN1	ENST00000264079.11	c.16G>A	p.Gly6Ser	missense_variant	Exon 1 of 14	1	NM_020533.3	ENSP00000264079.5
MCOLN1	ENST00000596390.1	n.132G>A		non_coding_transcript_exon_variant	Exon 1 of 2	1
MCOLN1	ENST00000601003.1	c.16G>A	p.Gly6Ser	missense_variant	Exon 1 of 5	3		ENSP00000469074.1
MCOLN1	ENST00000394321.9	n.96G>A		non_coding_transcript_exon_variant	Exon 1 of 13	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1257134 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 612910

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.14
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.61	T;T
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	-0.34	N;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.17	N;.
REVEL	Benign	0.28
Sift	Benign	0.18	T;.
Sift4G	Uncertain	0.042	D;T
Polyphen		0.29	B;.
Vest4		0.12
MutPred		0.36		Gain of glycosylation at G6 (P = 0.0044);Gain of glycosylation at G6 (P = 0.0044);
MVP		0.78
MPC		0.43
ClinPred		0.57	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.13
gMVP		0.33

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: rs61736595; hg19: chr19-7587652;