chr17-8173349-T-G

Position:

• chr17-8173349-T-G

Variant summary

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

The ENST00000437139.7(TMEM107):​c.*854A>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 0.179 in 609,538 control chromosomes in the GnomAD database, including 11,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2435 hom., cov: 34)
  • Exomes 𝑓: 0.18 (8924 hom.)
• Consequence: TMEM107 ENST00000437139.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.738

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 17-8173349-T-G is Benign according to our data. Variant chr17-8173349-T-G is described in ClinVar as [Benign]. Clinvar id is 1225279.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	Protein	UniProt
TMEM107	NM_183065.4	c.*854A>C		3_prime_UTR_variant	5/5	ENST00000437139.7	NP_898888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM107	ENST00000437139.7	c.*854A>C		3_prime_UTR_variant	5/5	1	NM_183065.4	ENSP00000402732	P1
TMEM107	ENST00000449985.6	c.*903A>C		3_prime_UTR_variant	2/2	1		ENSP00000404753

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24856 AN: 151894 Hom.: 2435 Cov.: 34

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0372

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.170

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.185 AC: 84544 AN: 457526 Hom.: 8924 Cov.: 0 AF XY: 0.186 AC XY: 45702 AN XY: 245956

Gnomad4 AFR exome AF: 0.0740

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.0275

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.164 AC: 24867 AN: 152012 Hom.: 2435 Cov.: 34 AF XY: 0.159 AC XY: 11799 AN XY: 74336

Gnomad4 AFR AF: 0.0779

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.0369

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.157

Alfa AF: 0.0933 Hom.: 160

Bravo AF: 0.162

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.0
DANN	Benign	0.27

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs79224651; hg19: chr17-8076667; COSMIC: COSV57101997; COSMIC: COSV57101997;