17-8173451-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

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 (★).

• Frequency:
  • Genomes: 𝑓 0.00091 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (1 hom.)
• Consequence: TMEM107 NM_183065.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.648

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 Likely_benign. Variant got -2 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 criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM107	NM_183065.4	c.*752T>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.*752T>C		3_prime_UTR_variant	5/5	1	NM_183065.4	P1
TMEM107	ENST00000449985.6	c.*801T>C		3_prime_UTR_variant	2/2	1
SNORD118	ENST00000363593.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.000907 AC: 138 AN: 152222 Hom.: 0 Cov.: 33

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.: 1 AF XY: 0.000768 AC XY: 98 AN XY: 127594

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.: 1 Cov.: 0 AF XY: 0.00103 AC XY: 342 AN XY: 333590

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.: 0 Cov.: 33 AF XY: 0.000913 AC XY: 68 AN XY: 74500

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.: 0

Bravo AF: 0.000835

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TMEM107-related disorder Benign:1

Likely benign, criteria provided, single submitter

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

Other links and lift over

dbSNP: rs201373697; hg19: chr17-8076769;