ENST00000363593.2:n.58A>T

Variant names:

• chr17-8173531-T-A
• rs755495846
• ENST00000363593.2:n.58A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000363593.2(SNORD118):​n.58A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000784 in 765,312 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: SNORD118 ENST00000363593.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27
• Publications: 2 publications found

Genes affected

SNORD118 (HGNC:32952): (small nucleolar RNA, C/D box 118)

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]

TMEM107 Gene-Disease associations (from GenCC):

• Meckel syndrome 13

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• ciliopathy

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• orofaciodigital syndrome 16

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

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=-0.34).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000363593.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNORD118	NR_033294.2	MANE Select	n.58A>T		non_coding_transcript_exon	Exon 1 of 1
	TMEM107	NM_183065.4	MANE Select	c.*672A>T		3_prime_UTR	Exon 5 of 5	NP_898888.1
	TMEM107	NR_147092.2		n.923A>T		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNORD118	ENST00000363593.2	TSL:6 MANE Select	n.58A>T		non_coding_transcript_exon	Exon 1 of 1
	TMEM107	ENST00000437139.7	TSL:1 MANE Select	c.*672A>T		3_prime_UTR	Exon 5 of 5	ENSP00000402732.2
	TMEM107	ENST00000449985.6	TSL:1	c.*721A>T		3_prime_UTR	Exon 2 of 2	ENSP00000404753.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152162 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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000172 AC: 4 AN: 232096 AF XY: 0.0000312

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: 0.0000369

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000815 AC: 5 AN: 613150 Hom.: 0 Cov.: 0 AF XY: 0.0000119 AC XY: 4 AN XY: 335160

African (AFR) AF: 0.00 AC: 0 AN: 17690

American (AMR) AF: 0.00 AC: 0 AN: 43734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20984

East Asian (EAS) AF: 0.00 AC: 0 AN: 36064

South Asian (SAS) AF: 0.00 AC: 0 AN: 69790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4120

European-Non Finnish (NFE) AF: 0.0000143 AC: 5 AN: 350012

Other (OTH) AF: 0.00 AC: 0 AN: 33000

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74356

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		3.3
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: rs755495846; hg19: chr17-8076849;