17-8173443-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:2
• Conservation: PhyloP100: 3.23

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 -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 GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM107	NM_183065.4	c.*760G>T		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.*760G>T		3_prime_UTR_variant	5/5	1	NM_183065.4	P1
TMEM107	ENST00000449985.6	c.*809G>T		3_prime_UTR_variant	2/2	1
SNORD118	ENST00000363593.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00626 AC: 953 AN: 152146 Hom.: 10 Cov.: 33

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.: 3 AF XY: 0.00159 AC XY: 203 AN XY: 127526

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.: 1 Cov.: 0 AF XY: 0.00123 AC XY: 409 AN XY: 332932

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.: 10 Cov.: 33 AF XY: 0.00578 AC XY: 430 AN XY: 74452

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.: 0

Bravo AF: 0.00720

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 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	14
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

Other links and lift over

dbSNP: rs116395281; hg19: chr17-8076761;