17-8173469-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_183065.4(TMEM107):​c.*734A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 764,380 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 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

TMEM107
NM_183065.4 3_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.88
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=-0.44).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM107NM_183065.4 linkuse as main transcriptc.*734A>G 3_prime_UTR_variant 5/5 ENST00000437139.7 NP_898888.1
SNORD118NR_033294.2 linkuse as main transcriptn.120A>G non_coding_transcript_exon_variant 1/1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM107ENST00000437139.7 linkuse as main transcriptc.*734A>G 3_prime_UTR_variant 5/51 NM_183065.4 ENSP00000402732 P1Q6UX40-1
TMEM107ENST00000449985.6 linkuse as main transcriptc.*783A>G 3_prime_UTR_variant 2/21 ENSP00000404753
SNORD118ENST00000363593.1 linkuse as main transcriptn.119A>G non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152144
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000377
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000142
AC:
33
AN:
231908
Hom.:
0
AF XY:
0.000164
AC XY:
21
AN XY:
127946
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000876
Gnomad ASJ exome
AF:
0.000101
Gnomad EAS exome
AF:
0.000171
Gnomad SAS exome
AF:
0.000594
Gnomad FIN exome
AF:
0.000429
Gnomad NFE exome
AF:
0.0000184
Gnomad OTH exome
AF:
0.000170
GnomAD4 exome
AF:
0.000140
AC:
86
AN:
612236
Hom.:
0
Cov.:
0
AF XY:
0.000152
AC XY:
51
AN XY:
334680
show subpopulations
Gnomad4 AFR exome
AF:
0.0000566
Gnomad4 AMR exome
AF:
0.0000458
Gnomad4 ASJ exome
AF:
0.0000477
Gnomad4 EAS exome
AF:
0.000222
Gnomad4 SAS exome
AF:
0.000660
Gnomad4 FIN exome
AF:
0.000265
Gnomad4 NFE exome
AF:
0.0000343
Gnomad4 OTH exome
AF:
0.000121
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152144
Hom.:
0
Cov.:
33
AF XY:
0.000108
AC XY:
8
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000377
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000427
Hom.:
0
Bravo
AF:
0.0000264

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 15, 2022In 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1476725). This variant has not been reported in the literature in individuals affected with SNORD118-related conditions. This variant is present in population databases (rs758890705, gnomAD 0.05%). This variant occurs in the SNORD118 gene, which encodes an RNA molecule that does not result in a protein product. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
CADD
Benign
0.0090
DANN
Benign
0.59

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs758890705; hg19: chr17-8076787; API