Genetic Variant RTTN:c.4303-25_4303-11delTTTTTTTTTTTTTTT (chr18-70086694-TAAAAAAAAAAAAAAA-T) – ACMG Classification: Benign (-16 pts)

Variant summary

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

The NM_173630.4(RTTN):c.4303-25_4303-11delTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 416,628 control chromosomes in the GnomAD database, including 6,687 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 4884 hom., cov: 0)

Exomes 𝑓: 0.22 ( 6687 hom. )

Failed GnomAD Quality Control

Consequence

RTTN
NM_173630.4 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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 18-70086694-TAAAAAAAAAAAAAAA-T is Benign according to our data. Variant chr18-70086694-TAAAAAAAAAAAAAAA-T is described in ClinVar as [Benign]. Clinvar id is 403407.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-70086694-TAAAAAAAAAAAAAAA-T is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTTN	NM_173630.4 link	c.4303-25_4303-11delTTTTTTTTTTTTTTT		intron_variant	Intron 31 of 48	ENST00000640769.2	NP_775901.3	Q86VV8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTTN	ENST00000640769.2 link	c.4303-25_4303-11delTTTTTTTTTTTTTTT		intron_variant	Intron 31 of 48	2	NM_173630.4	ENSP00000491507.1		Q86VV8-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

29317

AN:

68748

Hom.:

4887

Cov.:

FAILED QC

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.364

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.625

Gnomad SAS

AF:

0.612

Gnomad FIN

AF:

0.502

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.445

Gnomad OTH

AF:

0.435

GnomAD3 exomes

AF:

0.0312

AC:

2835

AN:

90912

Hom.:

AF XY:

0.0283

AC XY:

1471

AN XY:

52036

show subpopulations

Gnomad AFR exome

AF:

0.0433

Gnomad AMR exome

AF:

0.0714

Gnomad ASJ exome

AF:

0.0272

Gnomad EAS exome

AF:

0.0611

Gnomad SAS exome

AF:

0.0308

Gnomad FIN exome

AF:

0.00194

Gnomad NFE exome

AF:

0.0226

Gnomad OTH exome

AF:

0.0471

GnomAD4 exome

AF:

0.218

AC:

90682

AN:

416628

Hom.:

6687

AF XY:

0.212

AC XY:

47589

AN XY:

224578

show subpopulations

Gnomad4 AFR exome

AF:

0.183

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.203

Gnomad4 EAS exome

AF:

0.277

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.180

Gnomad4 NFE exome

AF:

0.230

Gnomad4 OTH exome

AF:

0.243

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.426

AC:

29311

AN:

68778

Hom.:

4884

Cov.:

AF XY:

0.430

AC XY:

13081

AN XY:

30452

show subpopulations

Gnomad4 AFR

AF:

0.297

Gnomad4 AMR

AF:

0.503

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.624

Gnomad4 SAS

AF:

0.610

Gnomad4 FIN

AF:

0.502

Gnomad4 NFE

AF:

0.445

Gnomad4 OTH

AF:

0.434

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Aug 05, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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.

18-70086694-TAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAA

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