17-8173423-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_183065.4(TMEM107):c.*780T>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 0.182 in 756,082 control chromosomes in the GnomAD database, including 14,494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2445 hom., cov: 33)
  • Exomes 𝑓: 0.19 (12049 hom.)
• Consequence: TMEM107 NM_183065.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.325

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]

SNORD118 (HGNC:32952): (small nucleolar RNA, C/D box 118)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 17-8173423-A-G is Benign according to our data. Variant chr17-8173423-A-G is described in ClinVar as [Benign]. Clinvar id is 1245232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM107	NM_183065.4	c.*780T>C		3_prime_UTR_variant	5/5	ENST00000437139.7
SNORD118	NR_033294.2			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM107	ENST00000437139.7	c.*780T>C		3_prime_UTR_variant	5/5	1	NM_183065.4	P1
TMEM107	ENST00000449985.6	c.*829T>C		3_prime_UTR_variant	2/2	1
SNORD118	ENST00000363593.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24889 AN: 152138 Hom.: 2445 Cov.: 33

Gnomad AFR AF: 0.0776

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0371

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.158

GnomAD3 exomes AF: 0.170 AC: 38973 AN: 229610 Hom.: 3943 AF XY: 0.175 AC XY: 22248 AN XY: 126816

Gnomad AFR exome AF: 0.0735

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.217

Gnomad EAS exome AF: 0.0432

Gnomad SAS exome AF: 0.129

Gnomad FIN exome AF: 0.162

Gnomad NFE exome AF: 0.230

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.186 AC: 112492 AN: 603826 Hom.: 12049 Cov.: 0 AF XY: 0.187 AC XY: 61582 AN XY: 329398

Gnomad4 AFR exome AF: 0.0756

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.0290

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.164 AC: 24899 AN: 152256 Hom.: 2445 Cov.: 33 AF XY: 0.159 AC XY: 11808 AN XY: 74442

Gnomad4 AFR AF: 0.0777

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.0368

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.156

Alfa AF: 0.141 Hom.: 404

Bravo AF: 0.161

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

TMEM107-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 11, 2021

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

GeneDx

May 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	0.035
Dann	Benign	0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs72479723; hg19: chr17-8076741; COSMIC: COSV57102000; COSMIC: COSV57102000;