17-8173337-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_183065.4(TMEM107):​c.*866G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 575,800 control chromosomes in the GnomAD database, including 30,702 homozygotes. 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 0.26 ( 6497 hom., cov: 33)
Exomes 𝑓: 0.32 ( 24205 hom. )

Consequence

TMEM107
NM_183065.4 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.28

Publications

14 publications found
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)
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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM107NM_183065.4 linkc.*866G>A 3_prime_UTR_variant Exon 5 of 5 ENST00000437139.7 NP_898888.1 Q6UX40-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM107ENST00000437139.7 linkc.*866G>A 3_prime_UTR_variant Exon 5 of 5 1 NM_183065.4 ENSP00000402732.2 Q6UX40-1
TMEM107ENST00000449985.6 linkc.*915G>A 3_prime_UTR_variant Exon 2 of 2 1 ENSP00000404753.2 B2RDT5
SNORD118ENST00000363593.2 linkn.*115G>A downstream_gene_variant 6

Frequencies

GnomAD3 genomes
AF:
0.265
AC:
40229
AN:
151782
Hom.:
6500
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0963
Gnomad AMI
AF:
0.419
Gnomad AMR
AF:
0.200
Gnomad ASJ
AF:
0.265
Gnomad EAS
AF:
0.116
Gnomad SAS
AF:
0.201
Gnomad FIN
AF:
0.402
Gnomad MID
AF:
0.199
Gnomad NFE
AF:
0.375
Gnomad OTH
AF:
0.278
GnomAD4 exome
AF:
0.321
AC:
135943
AN:
423900
Hom.:
24205
Cov.:
0
AF XY:
0.319
AC XY:
72467
AN XY:
227160
show subpopulations
African (AFR)
AF:
0.0921
AC:
1089
AN:
11818
American (AMR)
AF:
0.159
AC:
3690
AN:
23218
Ashkenazi Jewish (ASJ)
AF:
0.264
AC:
3484
AN:
13214
East Asian (EAS)
AF:
0.133
AC:
4044
AN:
30454
South Asian (SAS)
AF:
0.214
AC:
8044
AN:
37526
European-Finnish (FIN)
AF:
0.406
AC:
12652
AN:
31156
Middle Eastern (MID)
AF:
0.225
AC:
411
AN:
1826
European-Non Finnish (NFE)
AF:
0.379
AC:
94958
AN:
250502
Other (OTH)
AF:
0.313
AC:
7571
AN:
24186
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
4068
8136
12203
16271
20339
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
464
928
1392
1856
2320
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.265
AC:
40218
AN:
151900
Hom.:
6497
Cov.:
33
AF XY:
0.261
AC XY:
19392
AN XY:
74228
show subpopulations
African (AFR)
AF:
0.0961
AC:
3978
AN:
41406
American (AMR)
AF:
0.199
AC:
3038
AN:
15254
Ashkenazi Jewish (ASJ)
AF:
0.265
AC:
919
AN:
3470
East Asian (EAS)
AF:
0.116
AC:
601
AN:
5170
South Asian (SAS)
AF:
0.201
AC:
962
AN:
4796
European-Finnish (FIN)
AF:
0.402
AC:
4243
AN:
10552
Middle Eastern (MID)
AF:
0.197
AC:
58
AN:
294
European-Non Finnish (NFE)
AF:
0.375
AC:
25457
AN:
67932
Other (OTH)
AF:
0.274
AC:
580
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1447
2893
4340
5786
7233
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
412
824
1236
1648
2060
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.338
Hom.:
11789
Bravo
AF:
0.242

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Mar 09, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
0.31
DANN
Benign
0.44
PhyloP100
-1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Mutation Taster
=100/0
polymorphism (auto)

Splicing

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

Publications

Other links and lift over

dbSNP: rs3202848; hg19: chr17-8076655; COSMIC: COSV57101011; COSMIC: COSV57101011; API