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GeneBe

1-85022166-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_018298.11(MCOLN3):c.1224G>A(p.Ala408=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,614,078 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

MCOLN3
NM_018298.11 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.77
Variant links:
Genes affected
MCOLN3 (HGNC:13358): (mucolipin TRP cation channel 3) This gene encodes one of members of the mucolipin cation channel proteins. Mutation studies of the highly similar protein in mice have shown that the protein is found in cochlea hair cells, and mutant mice show early-onset hearing loss and balance problems. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
DNAI3 (HGNC:30711): (dynein axonemal intermediate chain 3) Enables Arp2/3 complex binding activity. Involved in negative regulation of Arp2/3 complex-mediated actin nucleation and negative regulation of cell migration. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-85022166-C-T is Benign according to our data. Variant chr1-85022166-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638904.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.77 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MCOLN3NM_018298.11 linkuse as main transcriptc.1224G>A p.Ala408= synonymous_variant 11/13 ENST00000370589.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MCOLN3ENST00000370589.7 linkuse as main transcriptc.1224G>A p.Ala408= synonymous_variant 11/131 NM_018298.11 P1Q8TDD5-1
MCOLN3ENST00000341115.8 linkuse as main transcriptc.1056G>A p.Ala352= synonymous_variant 10/122 Q8TDD5-2
DNAI3ENST00000370596.5 linkuse as main transcriptc.-15+22828C>T intron_variant 5 A2Q8IWG1-2
MCOLN3ENST00000474447.1 linkuse as main transcriptn.1249G>A non_coding_transcript_exon_variant 2/42

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000821
AC:
125
AN:
152180
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00128
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000892
AC:
224
AN:
251250
Hom.:
2
AF XY:
0.000898
AC XY:
122
AN XY:
135790
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.000434
Gnomad ASJ exome
AF:
0.00576
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00122
Gnomad OTH exome
AF:
0.000816
GnomAD4 exome
AF:
0.00140
AC:
2047
AN:
1461780
Hom.:
2
Cov.:
31
AF XY:
0.00135
AC XY:
980
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.000388
Gnomad4 AMR exome
AF:
0.000470
Gnomad4 ASJ exome
AF:
0.00528
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.00160
Gnomad4 OTH exome
AF:
0.00147
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000821
AC:
125
AN:
152298
Hom.:
0
Cov.:
33
AF XY:
0.000645
AC XY:
48
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.00128
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00130
Hom.:
3
Bravo
AF:
0.000824
EpiCase
AF:
0.00125
EpiControl
AF:
0.00172

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2022MCOLN3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
Cadd
Benign
0.25
Dann
Benign
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148052305; hg19: chr1-85487849; API