Variant rs117735243 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_183065.4(TMEM107):c.*617C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00135 in 764,050 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 4 hom. )

Consequence

TMEM107
NM_183065.4 3_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:2

Conservation

PhyloP100: 4.07

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BS2

High Homozygotes in GnomAdExome4 at 4 AR 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/exons	MANE	Protein	UniProt
TMEM107	NM_183065.4 linkuse as main transcript	c.*617C>T		3_prime_UTR_variant	5/5	ENST00000437139.7	NP_898888.1
SNORD118	NR_033294.2 linkuse as main transcript	n.3C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM107	ENST00000437139.7 linkuse as main transcript	c.*617C>T	3_prime_UTR_variant	5/5	1	NM_183065.4	ENSP00000402732	P1	Q6UX40-1
TMEM107	ENST00000449985.6 linkuse as main transcript	c.*666C>T	3_prime_UTR_variant	2/2	1		ENSP00000404753
SNORD118	ENST00000363593.1 linkuse as main transcript	n.2C>T	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

197

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00528

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000956

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.00146

AC:

338

AN:

231102

Hom.:

AF XY:

0.00143

AC XY:

183

AN XY:

127566

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.000509

Gnomad EAS exome

AF:

0.00222

Gnomad SAS exome

AF:

0.00136

Gnomad FIN exome

AF:

0.00653

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.000853

GnomAD4 exome

AF:

0.00137

AC:

837

AN:

611866

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

454

AN XY:

334362

show subpopulations

Gnomad4 AFR exome

AF:

0.000906

Gnomad4 AMR exome

AF:

0.00122

Gnomad4 ASJ exome

AF:

0.000286

Gnomad4 EAS exome

AF:

0.00233

Gnomad4 SAS exome

AF:

0.00144

Gnomad4 FIN exome

AF:

0.00591

Gnomad4 NFE exome

AF:

0.000905

Gnomad4 OTH exome

AF:

0.00112

GnomAD4 genome

AF:

0.00129

AC:

197

AN:

152184

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00405

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00528

Gnomad4 NFE

AF:

0.000956

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000610

Hom.:

Bravo

AF:

0.000914

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Leukoencephalopathy with calcifications and cysts

Pathogenic:1Uncertain:1

Pathogenic, no assertion criteria provided	clinical testing	Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine	Apr 06, 2020	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Undiagnosed Diseases Network, NIH	Mar 12, 2018	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 03, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	SNORD118: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.85

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over