rs148052305

Variant names:

• chr1-85022166-C-T
• rs148052305
• NM_018298.11:c.1224G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_018298.11(MCOLN3):​c.1224G>A​(p.Ala408Ala) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.77
• Publications: 2 publications found

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]

ENSG00000295769 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-85022166-C-T is Benign according to our data. Variant chr1-85022166-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2638904.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.77 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018298.11. 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
	MCOLN3	NM_018298.11	MANE Select	c.1224G>A	p.Ala408Ala	synonymous	Exon 11 of 13	NP_060768.8
	MCOLN3	NM_001253693.2		c.1056G>A	p.Ala352Ala	synonymous	Exon 10 of 12	NP_001240622.1	Q8TDD5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCOLN3	ENST00000370589.7	TSL:1 MANE Select	c.1224G>A	p.Ala408Ala	synonymous	Exon 11 of 13	ENSP00000359621.1	Q8TDD5-1
	MCOLN3	ENST00000889288.1		c.1224G>A	p.Ala408Ala	synonymous	Exon 12 of 14	ENSP00000559347.1
	MCOLN3	ENST00000889289.1		c.1224G>A	p.Ala408Ala	synonymous	Exon 12 of 14	ENSP00000559348.1

Frequencies

GnomAD3 genomes AF: 0.000821 AC: 125 AN: 152180 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.000892 AC: 224 AN: 251250 AF XY: 0.000898

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 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

African (AFR) AF: 0.000388 AC: 13 AN: 33468

American (AMR) AF: 0.000470 AC: 21 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00528 AC: 138 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00160 AC: 1783 AN: 1111948

Other (OTH) AF: 0.00147 AC: 89 AN: 60394

GnomAD4 genome AF: 0.000821 AC: 125 AN: 152298 Hom.: 0 Cov.: 33 AF XY: 0.000645 AC XY: 48 AN XY: 74470

African (AFR) AF: 0.000241 AC: 10 AN: 41564

American (AMR) AF: 0.000327 AC: 5 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00128 AC: 87 AN: 68028

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00130 Hom.: 3

Bravo AF: 0.000824

EpiCase AF: 0.00125

EpiControl AF: 0.00172

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.25
DANN	Benign	0.82
PhyloP100		-3.8
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs148052305; hg19: chr1-85487849;