rs201787275

Variant names:

• chr17-8173444-G-A
• rs201787275
• NM_183065.4:c.*759C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-8173444-G-A
• chr17-8173444-G-C
• chr17-8173444-G-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 8P and 2B. PP5_Very_Strong BP4 BS2_Supporting

The NM_183065.4(TMEM107):​c.*759C>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 0.00199 in 761,870 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (3 hom.)
• Consequence: TMEM107 NM_183065.4 3_prime_UTR
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:11
• Conservation: PhyloP100: 2.65
• Publications: 2 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, Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PP5: Variant 17-8173444-G-A is Pathogenic according to our data. Variant chr17-8173444-G-A is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 265788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29). . Strength limited to SUPPORTING due to the PP5.
• BS2: High Homozygotes in GnomAdExome4 at 3 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.*759C>T		3_prime_UTR	Exon 5 of 5	NP_898888.1	Q6UX40-1
	TMEM107	NM_032354.5		c.*759C>T		3_prime_UTR	Exon 5 of 5	NP_115730.2
	TMEM107	NM_001351278.2		c.*759C>T		3_prime_UTR	Exon 5 of 5	NP_001338207.1	Q6UX40-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM107	ENST00000437139.7	TSL:1 MANE Select	c.*759C>T		3_prime_UTR	Exon 5 of 5	ENSP00000402732.2	Q6UX40-1
	TMEM107	ENST00000449985.6	TSL:1	c.*808C>T		3_prime_UTR	Exon 2 of 2	ENSP00000404753.2	B2RDT5
	SNORD118	ENST00000363593.2	TSL:6 MANE Select	n.*8C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.00172 AC: 261 AN: 152160 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00276

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00196 AC: 454 AN: 231218 AF XY: 0.00201

Gnomad AFR exome AF: 0.000790

Gnomad AMR exome AF: 0.000822

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.000285

Gnomad FIN exome AF: 0.000172

Gnomad NFE exome AF: 0.00320

Gnomad OTH exome AF: 0.00171

GnomAD4 exome AF: 0.00206 AC: 1254 AN: 609592 Hom.: 3 Cov.: 0 AF XY: 0.00204 AC XY: 680 AN XY: 333104

African (AFR) AF: 0.000851 AC: 15 AN: 17620

American (AMR) AF: 0.000827 AC: 36 AN: 43520

Ashkenazi Jewish (ASJ) AF: 0.0000955 AC: 2 AN: 20948

East Asian (EAS) AF: 0.000167 AC: 6 AN: 35994

South Asian (SAS) AF: 0.00164 AC: 114 AN: 69516

European-Finnish (FIN) AF: 0.000239 AC: 9 AN: 37724

Middle Eastern (MID) AF: 0.000653 AC: 2 AN: 3062

European-Non Finnish (NFE) AF: 0.00293 AC: 1020 AN: 348428

Other (OTH) AF: 0.00153 AC: 50 AN: 32780

GnomAD4 genome AF: 0.00171 AC: 260 AN: 152278 Hom.: 0 Cov.: 33 AF XY: 0.00150 AC XY: 112 AN XY: 74466

African (AFR) AF: 0.00111 AC: 46 AN: 41568

American (AMR) AF: 0.000720 AC: 11 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10604

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

European-Non Finnish (NFE) AF: 0.00275 AC: 187 AN: 68020

Other (OTH) AF: 0.00142 AC: 3 AN: 2106

Alfa AF: 0.000468 Hom.: 0

Bravo AF: 0.00193

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic/Likely pathogenic

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
5	-	-	Leukoencephalopathy with calcifications and cysts (5)
3	-	-	not provided (3)
1	-	-	Meckel syndrome 13;C4539729:Orofaciodigital syndrome 16 (1)
1	-	-	Meckel-Gruber syndrome (1)
1	-	-	Orofaciodigital syndrome 16 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=93/7	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs201787275; hg19: chr17-8076762;