rs117735243

Variant names:

• chr17-8173586-G-A
• rs117735243
• NM_183065.4:c.*617C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-8173586-G-A
• chr17-8173586-G-C
• chr17-8173586-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6 BS2_Supporting

The NM_183065.4(TMEM107):​c.*617C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00135 in 764,050 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (4 hom.)
• Consequence: TMEM107 NM_183065.4 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1 U:1 B:2
• Conservation: PhyloP100: 4.07
• Publications: 4 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 17-8173586-G-A is Benign according to our data. Variant chr17-8173586-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 522851.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR,Unknown geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.*617C>T		3_prime_UTR	Exon 5 of 5	NP_898888.1	Q6UX40-1
	SNORD118	NR_033294.2	MANE Select	n.3C>T		non_coding_transcript_exon	Exon 1 of 1
	TMEM107	NM_032354.5		c.*617C>T		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.*617C>T		3_prime_UTR	Exon 5 of 5	ENSP00000402732.2	Q6UX40-1
	TMEM107	ENST00000449985.6	TSL:1	c.*666C>T		3_prime_UTR	Exon 2 of 2	ENSP00000404753.2	B2RDT5
	SNORD118	ENST00000363593.2	TSL:6 MANE Select	n.3C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00130 AC: 197 AN: 152064 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00528

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000956

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.00146 AC: 338 AN: 231102 AF XY: 0.00143

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.000509

Gnomad EAS exome AF: 0.00222

Gnomad FIN exome AF: 0.00653

Gnomad NFE exome AF: 0.00110

Gnomad OTH exome AF: 0.000853

GnomAD4 exome AF: 0.00137 AC: 837 AN: 611866 Hom.: 4 Cov.: 0 AF XY: 0.00136 AC XY: 454 AN XY: 334362

African (AFR) AF: 0.000906 AC: 16 AN: 17662

American (AMR) AF: 0.00122 AC: 53 AN: 43564

Ashkenazi Jewish (ASJ) AF: 0.000286 AC: 6 AN: 20956

East Asian (EAS) AF: 0.00233 AC: 84 AN: 36028

South Asian (SAS) AF: 0.00144 AC: 100 AN: 69604

European-Finnish (FIN) AF: 0.00591 AC: 223 AN: 37734

Middle Eastern (MID) AF: 0.000483 AC: 2 AN: 4140

European-Non Finnish (NFE) AF: 0.000905 AC: 316 AN: 349234

Other (OTH) AF: 0.00112 AC: 37 AN: 32944

GnomAD4 genome AF: 0.00129 AC: 197 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.00141 AC XY: 105 AN XY: 74406

African (AFR) AF: 0.000818 AC: 34 AN: 41552

American (AMR) AF: 0.00111 AC: 17 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5190

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00528 AC: 56 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000956 AC: 65 AN: 67968

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.000610 Hom.: 0

Bravo AF: 0.000914

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
1	1	-	Leukoencephalopathy with calcifications and cysts (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.85
PhyloP100		4.1
Mutation Taster		=32/53	disease causing

Splicing

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

Other links and lift over

dbSNP: rs117735243; hg19: chr17-8076904; COSMIC: COSV100328727; COSMIC: COSV100328727;