Variant 18-70004058-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173630.4(RTTN):c.*93G>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 0.0805 in 871,694 control chromosomes in the GnomAD database, including 3,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.069 ( 464 hom., cov: 31)

Exomes 𝑓: 0.083 ( 2687 hom. )

Consequence

RTTN
NM_173630.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.78

Variant links:

Genes affected

RTTN (HGNC:18654): (rotatin) This gene encodes a large protein whose specific function is unknown. Absence of the orthologous protein in mouse results in embryonic lethality with deficient axial rotation, abnormal differentiation of the neural tube, and randomized looping of the heart tube during development. In human, mutations in this gene are associated with polymicrogyria with seizures. In human fibroblasts this protein localizes at the ciliary basal bodies. Given the intracellular localization of this protein and the phenotypic effects of mutations, this gene is suspected of playing a role in the maintenance of normal ciliary structure which in turn effects the developmental process of left-right organ specification, axial rotation, and perhaps notochord development. [provided by RefSeq, Jan 2013]

RTTN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant 18-70004058-C-T is Benign according to our data. Variant chr18-70004058-C-T is described in ClinVar as [Benign]. Clinvar id is 1221909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTTN	NM_173630.4 linkuse as main transcript	c.*93G>A		3_prime_UTR_variant	49/49	ENST00000640769.2	NP_775901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTTN	ENST00000640769.2 linkuse as main transcript	c.*93G>A		3_prime_UTR_variant	49/49	2	NM_173630.4	ENSP00000491507	P1	Q86VV8-1

Frequencies

GnomAD3 genomes

AF:

0.0687

AC:

10454

AN:

152106

Hom.:

464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0176

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.0669

Gnomad ASJ

AF:

0.0726

Gnomad EAS

AF:

0.0869

Gnomad SAS

AF:

0.0851

Gnomad FIN

AF:

0.0644

Gnomad MID

AF:

0.0382

Gnomad NFE

AF:

0.0975

Gnomad OTH

AF:

0.0695

GnomAD4 exome

AF:

0.0831

AC:

59755

AN:

719470

Hom.:

2687

Cov.:

AF XY:

0.0844

AC XY:

32219

AN XY:

381932

show subpopulations

Gnomad4 AFR exome

AF:

0.0159

Gnomad4 AMR exome

AF:

0.0429

Gnomad4 ASJ exome

AF:

0.0737

Gnomad4 EAS exome

AF:

0.0681

Gnomad4 SAS exome

AF:

0.0790

Gnomad4 FIN exome

AF:

0.0686

Gnomad4 NFE exome

AF:

0.0932

Gnomad4 OTH exome

AF:

0.0815

GnomAD4 genome

AF:

0.0687

AC:

10455

AN:

152224

Hom.:

464

Cov.:

AF XY:

0.0681

AC XY:

5071

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0175

Gnomad4 AMR

AF:

0.0668

Gnomad4 ASJ

AF:

0.0726

Gnomad4 EAS

AF:

0.0867

Gnomad4 SAS

AF:

0.0856

Gnomad4 FIN

AF:

0.0644

Gnomad4 NFE

AF:

0.0976

Gnomad4 OTH

AF:

0.0688

Alfa

AF:

0.0894

Hom.:

619

Bravo

AF:

0.0636

Asia WGS

AF:

0.0680

AC:

237

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.033

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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