NM_183065.4:c.*744T>G

Variant names:

• chr17-8173459-A-C
• rs754582308
• NM_183065.4:c.*744T>G

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.*744T>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00000327 in 611,786 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: TMEM107 NM_183065.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81
• 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=-0.39).

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.*744T>G		3_prime_UTR	Exon 5 of 5	NP_898888.1	Q6UX40-1
	SNORD118	NR_033294.2	MANE Select	n.130T>G		non_coding_transcript_exon	Exon 1 of 1
	TMEM107	NM_032354.5		c.*744T>G		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.*744T>G		3_prime_UTR	Exon 5 of 5	ENSP00000402732.2	Q6UX40-1
	TMEM107	ENST00000449985.6	TSL:1	c.*793T>G		3_prime_UTR	Exon 2 of 2	ENSP00000404753.2	B2RDT5
	SNORD118	ENST00000363593.2	TSL:6 MANE Select	n.130T>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000863 AC: 2 AN: 231804 AF XY: 0.0000156

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000184

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000327 AC: 2 AN: 611786 Hom.: 0 Cov.: 0 AF XY: 0.00000598 AC XY: 2 AN XY: 334442

African (AFR) AF: 0.00 AC: 0 AN: 17660

American (AMR) AF: 0.00 AC: 0 AN: 43664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20980

East Asian (EAS) AF: 0.00 AC: 0 AN: 36040

South Asian (SAS) AF: 0.00 AC: 0 AN: 69672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37750

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3416

European-Non Finnish (NFE) AF: 0.00000572 AC: 2 AN: 349708

Other (OTH) AF: 0.00 AC: 0 AN: 32896

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		3.8

Splicing

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

Other links and lift over

dbSNP: rs754582308; hg19: chr17-8076777;