Genetic Variant RTTN:c.4303-27_4303-11delTTTTTTTTTTTTTTTTT (chr18-70086694-TAAAAAAAAAAAAAAAAA-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_173630.4(RTTN):c.4303-27_4303-11delTTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 414,016 control chromosomes in the GnomAD database, including 402 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 0)

Exomes 𝑓: 0.085 ( 402 hom. )

Failed GnomAD Quality Control

Consequence

RTTN
NM_173630.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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 -10 ACMG points.

BP6

Variant 18-70086694-TAAAAAAAAAAAAAAAAA-T is Benign according to our data. Variant chr18-70086694-TAAAAAAAAAAAAAAAAA-T is described in ClinVar as [Benign]. Clinvar id is 516914.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTTN	NM_173630.4 link	c.4303-27_4303-11delTTTTTTTTTTTTTTTTT		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.4303-27_4303-11delTTTTTTTTTTTTTTTTT		intron_variant	Intron 31 of 48	2	NM_173630.4	ENSP00000491507.1		Q86VV8-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

68180

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000678

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000101

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0208

AC:

1895

AN:

90912

Hom.:

AF XY:

0.0185

AC XY:

962

AN XY:

52036

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.0460

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.0476

Gnomad SAS exome

AF:

0.0226

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.0150

Gnomad OTH exome

AF:

0.0299

GnomAD4 exome

AF:

0.0846

AC:

35019

AN:

414016

Hom.:

402

AF XY:

0.0841

AC XY:

18777

AN XY:

223208

show subpopulations

Gnomad4 AFR exome

AF:

0.0657

Gnomad4 AMR exome

AF:

0.0797

Gnomad4 ASJ exome

AF:

0.0788

Gnomad4 EAS exome

AF:

0.132

Gnomad4 SAS exome

AF:

0.0732

Gnomad4 FIN exome

AF:

0.0696

Gnomad4 NFE exome

AF:

0.0832

Gnomad4 OTH exome

AF:

0.0974

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000235

AC:

AN:

68208

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

AN XY:

30224

show subpopulations

Gnomad4 AFR

AF:

0.000744

Gnomad4 AMR

AF:

0.000183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000101

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 23, 2018

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-TAAAAAAAAAAAAAA

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