18-70086692-T-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_173630.4(RTTN):​c.4303-8A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000056 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

RTTN
NM_173630.4 splice_region, intron

Scores

2
Splicing: ADA: 0.00003186
2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.734
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 18-70086692-T-G is Benign according to our data. Variant chr18-70086692-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3349180.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RTTNNM_173630.4 linkc.4303-8A>C splice_region_variant, 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
RTTNENST00000640769.2 linkc.4303-8A>C splice_region_variant, intron_variant Intron 31 of 48 2 NM_173630.4 ENSP00000491507.1 Q86VV8-1

Frequencies

GnomAD3 genomes
AF:
0.0000555
AC:
1
AN:
18002
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000950
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000223
AC:
2
AN:
89732
Hom.:
0
AF XY:
0.0000192
AC XY:
1
AN XY:
52150
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000815
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000224
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000196
AC:
3
AN:
152706
Hom.:
0
Cov.:
0
AF XY:
0.0000237
AC XY:
2
AN XY:
84258
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000138
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000111
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000555
AC:
1
AN:
18002
Hom.:
0
Cov.:
0
AF XY:
0.000126
AC XY:
1
AN XY:
7948
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000950
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

RTTN-related disorder Benign:1
Apr 17, 2024
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
1.1
DANN
Benign
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000032
dbscSNV1_RF
Benign
0.0
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.

Other links and lift over

dbSNP: rs199597732; hg19: chr18-67753928; API