rs3202848

chr17-8173337-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_183065.4(TMEM107):c.*866G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 575,800 control chromosomes in the GnomAD database, including 30,702 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (6497 hom., cov: 33)
  • Exomes 𝑓: 0.32 (24205 hom.)
• Consequence: TMEM107 NM_183065.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.28

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 17-8173337-C-T is Benign according to our data. Variant chr17-8173337-C-T is described in ClinVar as [Benign]. Clinvar id is 1294573.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM107	NM_183065.4	c.*866G>A		3_prime_UTR_variant	5/5	ENST00000437139.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM107	ENST00000437139.7	c.*866G>A		3_prime_UTR_variant	5/5	1	NM_183065.4	P1
TMEM107	ENST00000449985.6	c.*915G>A		3_prime_UTR_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40229 AN: 151782 Hom.: 6500 Cov.: 33

Gnomad AFR AF: 0.0963

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.321 AC: 135943 AN: 423900 Hom.: 24205 Cov.: 0 AF XY: 0.319 AC XY: 72467 AN XY: 227160

Gnomad4 AFR exome AF: 0.0921

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.264

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.265 AC: 40218 AN: 151900 Hom.: 6497 Cov.: 33 AF XY: 0.261 AC XY: 19392 AN XY: 74228

Gnomad4 AFR AF: 0.0961

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.274

Alfa AF: 0.340 Hom.: 10180

Bravo AF: 0.242

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	0.31
Dann	Benign	0.44
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: rs3202848; hg19: chr17-8076655; COSMIC: COSV57101011; COSMIC: COSV57101011;