17-8173337-C-T

Variant names:

• chr17-8173337-C-T
• rs3202848
• NM_183065.4:c.*866G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.28
• Publications: 14 publications found

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)

SNORD118 Gene-Disease associations (from GenCC):

• leukoencephalopathy with calcifications and cysts

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• 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 rank	MANE	Protein	UniProt
TMEM107	NM_183065.4	c.*866G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000437139.7	NP_898888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM107	ENST00000437139.7	c.*866G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_183065.4	ENSP00000402732.2
TMEM107	ENST00000449985.6	c.*915G>A		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000404753.2
SNORD118	ENST00000363593.2	n.*115G>A		downstream_gene_variant		6

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

African (AFR) AF: 0.0921 AC: 1089 AN: 11818

American (AMR) AF: 0.159 AC: 3690 AN: 23218

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 3484 AN: 13214

East Asian (EAS) AF: 0.133 AC: 4044 AN: 30454

South Asian (SAS) AF: 0.214 AC: 8044 AN: 37526

European-Finnish (FIN) AF: 0.406 AC: 12652 AN: 31156

Middle Eastern (MID) AF: 0.225 AC: 411 AN: 1826

European-Non Finnish (NFE) AF: 0.379 AC: 94958 AN: 250502

Other (OTH) AF: 0.313 AC: 7571 AN: 24186

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

African (AFR) AF: 0.0961 AC: 3978 AN: 41406

American (AMR) AF: 0.199 AC: 3038 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 919 AN: 3470

East Asian (EAS) AF: 0.116 AC: 601 AN: 5170

South Asian (SAS) AF: 0.201 AC: 962 AN: 4796

European-Finnish (FIN) AF: 0.402 AC: 4243 AN: 10552

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25457 AN: 67932

Other (OTH) AF: 0.274 AC: 580 AN: 2114

Alfa AF: 0.338 Hom.: 11789

Bravo AF: 0.242

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.31
DANN	Benign	0.44
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3202848; hg19: chr17-8076655; COSMIC: COSV57101011; COSMIC: COSV57101011;