Variant 17-8173448-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_183065.4(TMEM107):c.*755C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000624 in 762,634 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00060 ( 1 hom. )

Consequence

TMEM107
NM_183065.4 3_prime_UTR

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.80

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 17-8173448-G-C is Pathogenic according to our data. Variant chr17-8173448-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 929264.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-8173448-G-C is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).. Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM107	NM_183065.4 linkuse as main transcript	c.*755C>G		3_prime_UTR_variant	5/5	ENST00000437139.7
SNORD118	NR_033294.2 linkuse as main transcript			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM107	ENST00000437139.7 linkuse as main transcript	c.*755C>G	3_prime_UTR_variant	5/5	1	NM_183065.4	P1	Q6UX40-1
TMEM107	ENST00000449985.6 linkuse as main transcript	c.*804C>G	3_prime_UTR_variant	2/2	1
SNORD118	ENST00000363593.1 linkuse as main transcript		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.000703

AC:

107

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000614

AC:

142

AN:

231158

Hom.:

AF XY:

0.000627

AC XY:

AN XY:

127574

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000323

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.0000569

Gnomad SAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.000172

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.000512

GnomAD4 exome

AF:

0.000605

AC:

369

AN:

610300

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

188

AN XY:

333566

show subpopulations

Gnomad4 AFR exome

AF:

0.000397

Gnomad4 AMR exome

AF:

0.000459

Gnomad4 ASJ exome

AF:

0.0000477

Gnomad4 EAS exome

AF:

0.0000278

Gnomad4 SAS exome

AF:

0.000302

Gnomad4 FIN exome

AF:

0.0000795

Gnomad4 NFE exome

AF:

0.000834

Gnomad4 OTH exome

AF:

0.000640

GnomAD4 genome

AF:

0.000702

AC:

107

AN:

152334

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000809

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000300

Hom.:

Bravo

AF:

0.000752

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Leukoencephalopathy with calcifications and cysts

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine

Apr 06, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

Cadd

Benign

9.4

Dann

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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