rs201787275

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_183065.4(TMEM107):c.*759C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 761,870 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 3 hom. )

Consequence

TMEM107
NM_183065.4 3_prime_UTR

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:9

Conservation

PhyloP100: 2.65

Publications

2 publications found

Variant links:

Genes affected

TMEM107 (HGNC:28128): (transmembrane protein 107) This gene encodes a transmembrane protein and component of the primary cilia transition zone. The encoded protein regulates ciliogenesis and ciliary protein composition. Human fibroblasts expressing a mutant allele of this gene exhibit reduced numbers of cilia, altered cilia length, and impaired sonic hedgehog signaling. In human patients, different mutations in this gene cause different ciliopathies, including Meckel-Gruber syndrome and orofaciodigital syndrome. [provided by RefSeq, May 2017]

TMEM107 links:

SNORD118 (HGNC:32952): (small nucleolar RNA, C/D box 118)

SNORD118 Gene-Disease associations (from GenCC):

leukoencephalopathy with calcifications and cysts
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

SNORD118 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BS2

High Homozygotes in GnomAdExome4 at 3 AR,Unknown geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM107	NM_183065.4 link	c.*759C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000437139.7	NP_898888.1	Q6UX40-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM107	ENST00000437139.7 link	c.*759C>T	3_prime_UTR_variant	Exon 5 of 5	1	NM_183065.4	ENSP00000402732.2	Q6UX40-1
TMEM107	ENST00000449985.6 link	c.*808C>T	3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000404753.2	B2RDT5
SNORD118	ENST00000363593.2 link	n.*8C>T	downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.00172

AC:

261

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00276

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00196

AC:

454

AN:

231218

AF XY:

0.00201

show subpopulations

Gnomad AFR exome

AF:

0.000790

Gnomad AMR exome

AF:

0.000822

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.000285

Gnomad FIN exome

AF:

0.000172

Gnomad NFE exome

AF:

0.00320

Gnomad OTH exome

AF:

0.00171

GnomAD4 exome

AF:

0.00206

AC:

1254

AN:

609592

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

680

AN XY:

333104

show subpopulations

African (AFR)

AF:

0.000851

AC:

AN:

17620

American (AMR)

AF:

0.000827

AC:

AN:

43520

Ashkenazi Jewish (ASJ)

AF:

0.0000955

AC:

AN:

20948

East Asian (EAS)

AF:

0.000167

AC:

AN:

35994

South Asian (SAS)

AF:

0.00164

AC:

114

AN:

69516

European-Finnish (FIN)

AF:

0.000239

AC:

AN:

37724

Middle Eastern (MID)

AF:

0.000653

AC:

AN:

3062

European-Non Finnish (NFE)

AF:

0.00293

AC:

1020

AN:

348428

Other (OTH)

AF:

0.00153

AC:

AN:

32780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

123

184

246

307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00171

AC:

260

AN:

152278

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

112

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

41568

American (AMR)

AF:

0.000720

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00103

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00275

AC:

187

AN:

68020

Other (OTH)

AF:

0.00142

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000468

Hom.:

Bravo

AF:

0.00193

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Leukoencephalopathy with calcifications and cysts

Pathogenic:5

Apr 06, 2020

Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 10, 2016

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Aug 25, 2023

HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:research

- -

Aug 07, 2023

3billion

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.192%). Predicted Consequence: Non-coding transcript non-coding variant. The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least 2 similarly affected unrelated individuals (PMID: 27571260 / 3billion dataset). Functional studies provide moderate evidence of the variant having a damaging effect on the gene or gene product (PMID: 27571260). The variant has been reported to be associated with SNORD118-related disorder (ClinVar ID: VCV000929273). Therefore, the variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. -

Jan 03, 2024

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Pathogenic:3

Apr 03, 2024

GeneDx

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Functional studies provide conflicting evidence, with one study suggesting this variant alters processing of the precursor U8 snoRNAs while another study suggests this variant is functional (PMID: 27571260, 32359472); Variant in a snoRNA that alters a C:G Watson-Crick base pair to a U:G wobble base pair in the 3' extension (PMID: 32359472); This variant is associated with the following publications: (PMID: 32359472, 33029936, 27571260, 34426522, 37761957, 36697224, 34937159, 34986804, 34220662, 32400930, 34380746, 31521395, 32358219, 31912665) -

Jun 15, 2022

Revvity Omics, Revvity

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SNORD118: PM3:Very Strong, PM2:Supporting, PS3:Supporting -

Meckel-Gruber syndrome

Pathogenic:1

Sep 27, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=93/7

disease causing (ClinVar)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs201787275

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over