rs545394298

Variant names:

• chr17-8173569-G-A
• rs545394298
• NM_183065.4:c.*634C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-8173569-G-A
• chr17-8173569-G-C
• chr17-8173569-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_183065.4(TMEM107):​c.*634C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0000405 in 764,750 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: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: TMEM107 NM_183065.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 4.07
• Publications: 3 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: G2P, PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).

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.*634C>T		3_prime_UTR	Exon 5 of 5	NP_898888.1
	SNORD118	NR_033294.2	MANE Select	n.20C>T		non_coding_transcript_exon	Exon 1 of 1
	TMEM107	NM_032354.5		c.*634C>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.*634C>T		3_prime_UTR	Exon 5 of 5	ENSP00000402732.2
	TMEM107	ENST00000449985.6	TSL:1	c.*683C>T		3_prime_UTR	Exon 2 of 2	ENSP00000404753.2
	SNORD118	ENST00000363593.2	TSL:6 MANE Select	n.20C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000302 AC: 7 AN: 231710 AF XY: 0.0000313

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000569

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000461

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000408 AC: 25 AN: 612598 Hom.: 0 Cov.: 0 AF XY: 0.0000358 AC XY: 12 AN XY: 334808

African (AFR) AF: 0.00 AC: 0 AN: 17672

American (AMR) AF: 0.00 AC: 0 AN: 43602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20976

East Asian (EAS) AF: 0.0000277 AC: 1 AN: 36054

South Asian (SAS) AF: 0.0000430 AC: 3 AN: 69708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4142

European-Non Finnish (NFE) AF: 0.0000515 AC: 18 AN: 349718

Other (OTH) AF: 0.0000910 AC: 3 AN: 32980

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74328

African (AFR) AF: 0.0000241 AC: 1 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	1	-	Leukoencephalopathy with calcifications and cysts (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	19
DANN	Benign	0.95
PhyloP100		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Other links and lift over

dbSNP: rs545394298; hg19: chr17-8076887;