Variant 17-8173451-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_183065.4(TMEM107):c.*752T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000994 in 762,688 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

TMEM107
NM_183065.4 3_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.648

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 -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 17-8173451-A-G is Benign according to our data. Variant chr17-8173451-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3031501.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM107	NM_183065.4 linkuse as main transcript	c.*752T>C		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.*752T>C	3_prime_UTR_variant	5/5	1	NM_183065.4	ENSP00000402732	P1	Q6UX40-1
TMEM107	ENST00000449985.6 linkuse as main transcript	c.*801T>C	3_prime_UTR_variant	2/2	1		ENSP00000404753
SNORD118	ENST00000363593.1 linkuse as main transcript		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.000907

AC:

138

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00173

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000748

AC:

173

AN:

231208

Hom.:

AF XY:

0.000768

AC XY:

AN XY:

127594

show subpopulations

Gnomad AFR exome

AF:

0.000287

Gnomad AMR exome

AF:

0.000323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000664

Gnomad FIN exome

AF:

0.000172

Gnomad NFE exome

AF:

0.00140

Gnomad OTH exome

AF:

0.000512

GnomAD4 exome

AF:

0.00102

AC:

620

AN:

610348

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

342

AN XY:

333590

show subpopulations

Gnomad4 AFR exome

AF:

0.000284

Gnomad4 AMR exome

AF:

0.000368

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000555

Gnomad4 SAS exome

AF:

0.0000431

Gnomad4 FIN exome

AF:

0.000212

Gnomad4 NFE exome

AF:

0.00158

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000906

AC:

138

AN:

152340

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00173

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00151

Hom.:

Bravo

AF:

0.000835

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TMEM107-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 31, 2021

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

-0.37

CADD

Benign

3.2

DANN

Benign

0.74

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