Variant 17-8173473-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_183065.4(TMEM107):c.*730C>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 0.00346 in 764,556 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 5 hom. )

Consequence

TMEM107
NM_183065.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.79

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]

TMEM107 links:

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

SNORD118 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 17-8173473-G-A is Benign according to our data. Variant chr17-8173473-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1599029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8173473-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM107	NM_183065.4 linkuse as main transcript	c.*730C>T		3_prime_UTR_variant	5/5	ENST00000437139.7	NP_898888.1
SNORD118	NR_033294.2 linkuse as main transcript	n.116C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM107	ENST00000437139.7 linkuse as main transcript	c.*730C>T	3_prime_UTR_variant	5/5	1	NM_183065.4	ENSP00000402732	P1	Q6UX40-1
TMEM107	ENST00000449985.6 linkuse as main transcript	c.*779C>T	3_prime_UTR_variant	2/2	1		ENSP00000404753
SNORD118	ENST00000363593.1 linkuse as main transcript	n.115C>T	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00346

AC:

527

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00236

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00443

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00378

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00322

AC:

746

AN:

231908

Hom.:

AF XY:

0.00324

AC XY:

414

AN XY:

127956

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00341

Gnomad SAS exome

AF:

0.000792

Gnomad FIN exome

AF:

0.00807

Gnomad NFE exome

AF:

0.00443

Gnomad OTH exome

AF:

0.00306

GnomAD4 exome

AF:

0.00346

AC:

2120

AN:

612324

Hom.:

Cov.:

AF XY:

0.00338

AC XY:

1133

AN XY:

334742

show subpopulations

Gnomad4 AFR exome

AF:

0.00204

Gnomad4 AMR exome

AF:

0.00137

Gnomad4 ASJ exome

AF:

0.0000477

Gnomad4 EAS exome

AF:

0.00194

Gnomad4 SAS exome

AF:

0.000818

Gnomad4 FIN exome

AF:

0.00887

Gnomad4 NFE exome

AF:

0.00414

Gnomad4 OTH exome

AF:

0.00334

GnomAD4 genome

AF:

0.00346

AC:

527

AN:

152232

Hom.:

Cov.:

AF XY:

0.00378

AC XY:

281

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00238

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00444

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0105

Gnomad4 NFE

AF:

0.00378

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.00265

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	SNORD118: BS2; TMEM107: BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

7.2

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over