17-8173455-T-G

Variant names:

• chr17-8173455-T-G
• rs758058586
• NM_183065.4:c.*748A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_183065.4(TMEM107):​c.*748A>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 0.00000982 in 610,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: TMEM107 NM_183065.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.27
• Publications: 0 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: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183065.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM107	NM_183065.4	MANE Select	c.*748A>C		3_prime_UTR	Exon 5 of 5	NP_898888.1	Q6UX40-1
	SNORD118	NR_033294.2	MANE Select	n.134A>C		non_coding_transcript_exon	Exon 1 of 1
	TMEM107	NM_032354.5		c.*748A>C		3_prime_UTR	Exon 5 of 5	NP_115730.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM107	ENST00000437139.7	TSL:1 MANE Select	c.*748A>C		3_prime_UTR	Exon 5 of 5	ENSP00000402732.2	Q6UX40-1
	TMEM107	ENST00000449985.6	TSL:1	c.*797A>C		3_prime_UTR	Exon 2 of 2	ENSP00000404753.2	B2RDT5
	SNORD118	ENST00000363593.2	TSL:6 MANE Select	n.134A>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000259 AC: 6 AN: 231412 AF XY: 0.0000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000924

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000982 AC: 6 AN: 610930 Hom.: 0 Cov.: 0 AF XY: 0.00000599 AC XY: 2 AN XY: 333934

African (AFR) AF: 0.00 AC: 0 AN: 17626

American (AMR) AF: 0.0000918 AC: 4 AN: 43556

Ashkenazi Jewish (ASJ) AF: 0.0000477 AC: 1 AN: 20974

East Asian (EAS) AF: 0.00 AC: 0 AN: 36018

South Asian (SAS) AF: 0.00 AC: 0 AN: 69576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3328

European-Non Finnish (NFE) AF: 0.00000286 AC: 1 AN: 349256

Other (OTH) AF: 0.00 AC: 0 AN: 32856

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	9.3
DANN	Benign	0.76
PhyloP100		3.3
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

Other links and lift over

dbSNP: rs758058586; hg19: chr17-8076773;