Variant 17-8173443-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_183065.4(TMEM107):c.*760G>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 0.00236 in 761,446 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 1 hom. )

Consequence

TMEM107
NM_183065.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:3

Conservation

PhyloP100: 3.23

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00628 (956/152262) while in subpopulation AFR AF= 0.0199 (825/41554). AF 95% confidence interval is 0.0187. There are 10 homozygotes in gnomad4. There are 430 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM107	NM_183065.4 linkuse as main transcript	c.*760G>T		3_prime_UTR_variant	5/5	ENST00000437139.7	NP_898888.1
SNORD118	NR_033294.2 linkuse as main transcript			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM107	ENST00000437139.7 linkuse as main transcript	c.*760G>T	3_prime_UTR_variant	5/5	1	NM_183065.4	ENSP00000402732	P1	Q6UX40-1
TMEM107	ENST00000449985.6 linkuse as main transcript	c.*809G>T	3_prime_UTR_variant	2/2	1		ENSP00000404753
SNORD118	ENST00000363593.1 linkuse as main transcript		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.00626

AC:

953

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00200

AC:

462

AN:

231110

Hom.:

AF XY:

0.00159

AC XY:

203

AN XY:

127526

show subpopulations

Gnomad AFR exome

AF:

0.0217

Gnomad AMR exome

AF:

0.000558

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000332

Gnomad FIN exome

AF:

0.000258

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.00139

AC:

844

AN:

609184

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

409

AN XY:

332932

show subpopulations

Gnomad4 AFR exome

AF:

0.0187

Gnomad4 AMR exome

AF:

0.000483

Gnomad4 ASJ exome

AF:

0.0000478

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000345

Gnomad4 FIN exome

AF:

0.000452

Gnomad4 NFE exome

AF:

0.00115

Gnomad4 OTH exome

AF:

0.00150

GnomAD4 genome

AF:

0.00628

AC:

956

AN:

152262

Hom.:

Cov.:

AF XY:

0.00578

AC XY:

430

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0199

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.000577

Hom.:

Bravo

AF:

0.00720

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

TMEM107-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 16, 2024

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

SNORD118: BS1, BS2; TMEM107: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.80

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