rs201884120

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_173630.4(RTTN):​c.80G>T​(p.Cys27Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RTTN
NM_173630.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.64
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27241397).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RTTNNM_173630.4 linkc.80G>T p.Cys27Phe missense_variant Exon 2 of 49 ENST00000640769.2 NP_775901.3 Q86VV8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RTTNENST00000640769.2 linkc.80G>T p.Cys27Phe missense_variant Exon 2 of 49 2 NM_173630.4 ENSP00000491507.1 Q86VV8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461892
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
20
DANN
Benign
0.93
DEOGEN2
Benign
0.18
T;.
Eigen
Benign
-0.064
Eigen_PC
Benign
0.11
FATHMM_MKL
Benign
0.41
N
LIST_S2
Benign
0.79
T;T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.27
T;T
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
0.90
L;L
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.4
.;N
REVEL
Benign
0.083
Sift
Benign
0.22
.;T
Sift4G
Benign
0.24
.;T
Polyphen
0.13
B;.
Vest4
0.22
MutPred
0.71
Loss of methylation at K28 (P = 0.0531);Loss of methylation at K28 (P = 0.0531);
MVP
0.38
MPC
0.11
ClinPred
0.70
D
GERP RS
5.5
Varity_R
0.22
gMVP
0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-67872503; COSMIC: COSV99733837; COSMIC: COSV99733837; API