chr17-8173474-G-A

Position:

• chr17-8173474-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_183065.4(TMEM107):​c.*729C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000714 in 764,652 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00074 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00071 (1 hom.)
• Consequence: TMEM107 NM_183065.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.864

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)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM107	NM_183065.4	c.*729C>T		3_prime_UTR_variant	5/5	ENST00000437139.7	NP_898888.1
SNORD118	NR_033294.2	n.115C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM107	ENST00000437139.7	c.*729C>T		3_prime_UTR_variant	5/5	1	NM_183065.4	ENSP00000402732	P1
TMEM107	ENST00000449985.6	c.*778C>T		3_prime_UTR_variant	2/2	1		ENSP00000404753
SNORD118	ENST00000363593.1	n.114C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.000743 AC: 113 AN: 152130 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.000711 AC: 165 AN: 231946 Hom.: 1 AF XY: 0.000789 AC XY: 101 AN XY: 127970

Gnomad AFR exome AF: 0.000932

Gnomad AMR exome AF: 0.000875

Gnomad ASJ exome AF: 0.000710

Gnomad EAS exome AF: 0.000284

Gnomad SAS exome AF: 0.000825

Gnomad FIN exome AF: 0.000429

Gnomad NFE exome AF: 0.000627

Gnomad OTH exome AF: 0.00204

GnomAD4 exome AF: 0.000707 AC: 433 AN: 612404 Hom.: 1 Cov.: 0 AF XY: 0.000786 AC XY: 263 AN XY: 334780

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.000961

Gnomad4 ASJ exome AF: 0.000810

Gnomad4 EAS exome AF: 0.00208

Gnomad4 SAS exome AF: 0.000875

Gnomad4 FIN exome AF: 0.000265

Gnomad4 NFE exome AF: 0.000514

Gnomad4 OTH exome AF: 0.000789

GnomAD4 genome AF: 0.000742 AC: 113 AN: 152248 Hom.: 0 Cov.: 33 AF XY: 0.000806 AC XY: 60 AN XY: 74442

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000251 Hom.: 0

Bravo AF: 0.000695

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	This variant occurs in the SNORD118 gene, which encodes an RNA molecule that does not result in a protein product. This variant is present in population databases (rs148801759, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with SNORD118-related conditions. ClinVar contains an entry for this variant (Variation ID: 1510987). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	3.7
DANN	Benign	0.69
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: rs148801759; hg19: chr17-8076792;