Variant chr17-8173470-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_183065.4(TMEM107):c.*733G>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 0.0000288 in 764,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

TMEM107
NM_183065.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM107	NM_183065.4 linkuse as main transcript	c.*733G>C		3_prime_UTR_variant	5/5	ENST00000437139.7	NP_898888.1
SNORD118	NR_033294.2 linkuse as main transcript	n.119G>C		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.*733G>C	3_prime_UTR_variant	5/5	1	NM_183065.4	ENSP00000402732	P1	Q6UX40-1
TMEM107	ENST00000449985.6 linkuse as main transcript	c.*782G>C	3_prime_UTR_variant	2/2	1		ENSP00000404753
SNORD118	ENST00000363593.1 linkuse as main transcript	n.118G>C	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000129

AC:

AN:

231890

Hom.:

AF XY:

0.0000156

AC XY:

AN XY:

127938

show subpopulations

Gnomad AFR exome

AF:

0.0000717

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000922

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000310

AC:

AN:

612240

Hom.:

Cov.:

AF XY:

0.0000359

AC XY:

AN XY:

334682

show subpopulations

Gnomad4 AFR exome

AF:

0.0000566

Gnomad4 AMR exome

AF:

0.0000229

Gnomad4 ASJ exome

AF:

0.0000477

Gnomad4 EAS exome

AF:

0.0000277

Gnomad4 SAS exome

AF:

0.0000430

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000314

Gnomad4 OTH exome

AF:

0.0000304

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 22, 2023

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1356857). This variant has not been reported in the literature in individuals affected with SNORD118-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant occurs in the SNORD118 gene, which encodes an RNA molecule that does not result in a protein product. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.63

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