rs117183725

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_173630.4(RTTN):c.6015C>T(p.Ala2005Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00905 in 1,613,954 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0094 ( 90 hom. )

Consequence

RTTN
NM_173630.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.395

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 18-70020753-G-A is Benign according to our data. Variant chr18-70020753-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 212085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-70020753-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.395 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00602 (917/152284) while in subpopulation NFE AF= 0.00926 (630/68022). AF 95% confidence interval is 0.00866. There are 3 homozygotes in gnomad4. There are 448 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTTN	NM_173630.4 link	c.6015C>T	p.Ala2005Ala	synonymous_variant	Exon 45 of 49	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.6015C>T	p.Ala2005Ala	synonymous_variant	Exon 45 of 49	2	NM_173630.4	ENSP00000491507.1		Q86VV8-1

Frequencies

GnomAD3 genomes

AF:

0.00604

AC:

919

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00850

Gnomad FIN

AF:

0.00443

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00926

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00704

AC:

1753

AN:

248862

Hom.:

AF XY:

0.00748

AC XY:

1010

AN XY:

134976

show subpopulations

Gnomad AFR exome

AF:

0.00161

Gnomad AMR exome

AF:

0.00389

Gnomad ASJ exome

AF:

0.00607

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0104

Gnomad FIN exome

AF:

0.00640

Gnomad NFE exome

AF:

0.00900

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.00936

AC:

13688

AN:

1461670

Hom.:

Cov.:

AF XY:

0.00935

AC XY:

6796

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00218

Gnomad4 AMR exome

AF:

0.00394

Gnomad4 ASJ exome

AF:

0.00609

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0100

Gnomad4 FIN exome

AF:

0.00689

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00931

GnomAD4 genome

AF:

0.00602

AC:

917

AN:

152284

Hom.:

Cov.:

AF XY:

0.00602

AC XY:

448

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00809

Gnomad4 FIN

AF:

0.00443

Gnomad4 NFE

AF:

0.00926

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00787

Hom.:

Bravo

AF:

0.00597

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.00999

EpiControl

AF:

0.00860

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RTTN: BP4, BP7, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:2

Aug 01, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Feb 07, 2018

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.9

DANN

Benign

0.42

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