Variant 17-8173452-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_183065.4(TMEM107):c.*751C>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 0.00562 in 762,922 control chromosomes in the GnomAD database, including 26 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 0.0045 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0059 ( 25 hom. )

Consequence

TMEM107
NM_183065.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.74

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BS2

High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM107	NM_183065.4 linkuse as main transcript	c.*751C>T		3_prime_UTR_variant	5/5	ENST00000437139.7
SNORD118	NR_033294.2 linkuse as main transcript	n.137C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM107	ENST00000437139.7 linkuse as main transcript	c.*751C>T	3_prime_UTR_variant	5/5	1	NM_183065.4	P1	Q6UX40-1
TMEM107	ENST00000449985.6 linkuse as main transcript	c.*800C>T	3_prime_UTR_variant	2/2	1
SNORD118	ENST00000363593.1 linkuse as main transcript		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.00455

AC:

692

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00434

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00754

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00484

AC:

1120

AN:

231386

Hom.:

AF XY:

0.00459

AC XY:

586

AN XY:

127682

show subpopulations

Gnomad AFR exome

AF:

0.00158

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.0155

Gnomad EAS exome

AF:

0.000683

Gnomad SAS exome

AF:

0.00179

Gnomad FIN exome

AF:

0.00696

Gnomad NFE exome

AF:

0.00633

Gnomad OTH exome

AF:

0.00460

GnomAD4 exome

AF:

0.00588

AC:

3592

AN:

610650

Hom.:

Cov.:

AF XY:

0.00574

AC XY:

1915

AN XY:

333762

show subpopulations

Gnomad4 AFR exome

AF:

0.00181

Gnomad4 AMR exome

AF:

0.00266

Gnomad4 ASJ exome

AF:

0.0154

Gnomad4 EAS exome

AF:

0.000444

Gnomad4 SAS exome

AF:

0.00218

Gnomad4 FIN exome

AF:

0.00603

Gnomad4 NFE exome

AF:

0.00732

Gnomad4 OTH exome

AF:

0.00512

GnomAD4 genome

AF:

0.00454

AC:

692

AN:

152272

Hom.:

Cov.:

AF XY:

0.00443

AC XY:

330

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00249

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00434

Gnomad4 NFE

AF:

0.00754

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00599

Hom.:

Bravo

AF:

0.00413

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

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

Leukoencephalopathy with calcifications and cysts

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine

Apr 06, 2020

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

TMEM107-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 31, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

Cadd

Benign

Dann

Benign

0.81

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