Variant 17-8173460-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_183065.4(TMEM107):c.*743G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 762,934 control chromosomes in the GnomAD database, including 173,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33780 hom., cov: 33)

Exomes 𝑓: 0.67 ( 139960 hom. )

Consequence

TMEM107
NM_183065.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.55

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 17-8173460-C-T is Benign according to our data. Variant chr17-8173460-C-T is described in ClinVar as [Benign]. Clinvar id is 1168310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM107	NM_183065.4 linkuse as main transcript	c.*743G>A		3_prime_UTR_variant	5/5	ENST00000437139.7	NP_898888.1
SNORD118	NR_033294.2 linkuse as main transcript	n.129G>A		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.*743G>A	3_prime_UTR_variant	5/5	1	NM_183065.4	ENSP00000402732	P1	Q6UX40-1
TMEM107	ENST00000449985.6 linkuse as main transcript	c.*792G>A	3_prime_UTR_variant	2/2	1		ENSP00000404753
SNORD118	ENST00000363593.1 linkuse as main transcript	n.128G>A	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.665

AC:

100869

AN:

151714

Hom.:

33756

Cov.:

show subpopulations

Gnomad AFR

AF:

0.637

Gnomad AMI

AF:

0.626

Gnomad AMR

AF:

0.694

Gnomad ASJ

AF:

0.490

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.728

Gnomad FIN

AF:

0.779

Gnomad MID

AF:

0.580

Gnomad NFE

AF:

0.676

Gnomad OTH

AF:

0.646

GnomAD3 exomes

AF:

0.668

AC:

154482

AN:

231344

Hom.:

52314

AF XY:

0.668

AC XY:

85277

AN XY:

127702

show subpopulations

Gnomad AFR exome

AF:

0.630

Gnomad AMR exome

AF:

0.729

Gnomad ASJ exome

AF:

0.510

Gnomad EAS exome

AF:

0.474

Gnomad SAS exome

AF:

0.716

Gnomad FIN exome

AF:

0.769

Gnomad NFE exome

AF:

0.676

Gnomad OTH exome

AF:

0.652

GnomAD4 exome

AF:

0.673

AC:

411154

AN:

611100

Hom.:

139960

Cov.:

AF XY:

0.674

AC XY:

225037

AN XY:

334022

show subpopulations

Gnomad4 AFR exome

AF:

0.633

Gnomad4 AMR exome

AF:

0.724

Gnomad4 ASJ exome

AF:

0.512

Gnomad4 EAS exome

AF:

0.525

Gnomad4 SAS exome

AF:

0.716

Gnomad4 FIN exome

AF:

0.772

Gnomad4 NFE exome

AF:

0.677

Gnomad4 OTH exome

AF:

0.652

GnomAD4 genome

AF:

0.665

AC:

100940

AN:

151834

Hom.:

33780

Cov.:

AF XY:

0.670

AC XY:

49722

AN XY:

74190

show subpopulations

Gnomad4 AFR

AF:

0.637

Gnomad4 AMR

AF:

0.694

Gnomad4 ASJ

AF:

0.490

Gnomad4 EAS

AF:

0.500

Gnomad4 SAS

AF:

0.727

Gnomad4 FIN

AF:

0.779

Gnomad4 NFE

AF:

0.676

Gnomad4 OTH

AF:

0.644

Alfa

AF:

0.604

Hom.:

4002

Bravo

AF:

0.654

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 19, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

TMEM107-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 22, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.0010

DANN

Benign

0.76

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