Variant 18-70086694-TAAAAAAAAAAAAAAAA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_173630.4(RTTN):c.4303-26_4303-11del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 415,838 control chromosomes in the GnomAD database, including 3,224 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 13 hom., cov: 0)

Exomes 𝑓: 0.18 ( 3224 hom. )

Failed GnomAD Quality Control

Consequence

RTTN
NM_173630.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 2.23

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 -16 ACMG points.

BP6

Variant 18-70086694-TAAAAAAAAAAAAAAAA-T is Benign according to our data. Variant chr18-70086694-TAAAAAAAAAAAAAAAA-T is described in ClinVar as [Benign]. Clinvar id is 403408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 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.4303-26_4303-11del		splice_polypyrimidine_tract_variant, intron_variant		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.4303-26_4303-11del		splice_polypyrimidine_tract_variant, intron_variant		2	NM_173630.4	ENSP00000491507	P1	Q86VV8-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

878

AN:

68214

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0207

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.000932

Gnomad EAS

AF:

0.0301

Gnomad SAS

AF:

0.0250

Gnomad FIN

AF:

0.00174

Gnomad MID

AF:

0.00926

Gnomad NFE

AF:

0.00952

Gnomad OTH

AF:

0.0132

GnomAD3 exomes

AF:

0.0391

AC:

3558

AN:

90912

Hom.:

AF XY:

0.0351

AC XY:

1828

AN XY:

52036

show subpopulations

Gnomad AFR exome

AF:

0.0447

Gnomad AMR exome

AF:

0.0842

Gnomad ASJ exome

AF:

0.0313

Gnomad EAS exome

AF:

0.0961

Gnomad SAS exome

AF:

0.0368

Gnomad FIN exome

AF:

0.00338

Gnomad NFE exome

AF:

0.0280

Gnomad OTH exome

AF:

0.0617

GnomAD4 exome

AF:

0.178

AC:

74030

AN:

415838

Hom.:

3224

AF XY:

0.176

AC XY:

39364

AN XY:

224122

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.165

Gnomad4 EAS exome

AF:

0.241

Gnomad4 SAS exome

AF:

0.141

Gnomad4 FIN exome

AF:

0.145

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0129

AC:

881

AN:

68242

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

396

AN XY:

30244

show subpopulations

Gnomad4 AFR

AF:

0.0206

Gnomad4 AMR

AF:

0.0147

Gnomad4 ASJ

AF:

0.000932

Gnomad4 EAS

AF:

0.0301

Gnomad4 SAS

AF:

0.0252

Gnomad4 FIN

AF:

0.00174

Gnomad4 NFE

AF:

0.00952

Gnomad4 OTH

AF:

0.0142

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 18, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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