17-8173440-G-A

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.*763C>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 0.000535 in 761,194 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 0.0015 (1 hom., cov: 34)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: TMEM107 NM_183065.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.49

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=-0.31).
• BP6: Variant 17-8173440-G-A is Benign according to our data. Variant chr17-8173440-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3029994.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.*763C>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.*763C>T		3_prime_UTR_variant	5/5	1	NM_183065.4	P1
TMEM107	ENST00000449985.6	c.*812C>T		3_prime_UTR_variant	2/2	1
SNORD118	ENST00000363593.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 229 AN: 152184 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00442

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000437 AC: 101 AN: 231166 Hom.: 0 AF XY: 0.000345 AC XY: 44 AN XY: 127562

Gnomad AFR exome AF: 0.00517

Gnomad AMR exome AF: 0.0000588

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000399

Gnomad SAS exome AF: 0.0000664

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000157

Gnomad OTH exome AF: 0.000171

GnomAD4 exome AF: 0.000287 AC: 175 AN: 608892 Hom.: 0 Cov.: 0 AF XY: 0.000271 AC XY: 90 AN XY: 332568

Gnomad4 AFR exome AF: 0.00488

Gnomad4 AMR exome AF: 0.000161

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000139

Gnomad4 SAS exome AF: 0.000101

Gnomad4 FIN exome AF: 0.0000265

Gnomad4 NFE exome AF: 0.000138

Gnomad4 OTH exome AF: 0.000611

GnomAD4 genome AF: 0.00152 AC: 232 AN: 152302 Hom.: 1 Cov.: 34 AF XY: 0.00168 AC XY: 125 AN XY: 74476

Gnomad4 AFR AF: 0.00447

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.0000428 Hom.: 0

Bravo AF: 0.00146

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

Feb 18, 2022

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	-0.31
Cadd	Benign	4.1
Dann	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs377665716; hg19: chr17-8076758; COSMIC: COSV57100852; COSMIC: COSV57100852;