Genetic Variant RTTN:c.4303-30_4303-11delTTTTTTTTTTTTTTTTTTTT (chr18-70086694-TAAAAAAAAAAAAAAAAAAAA-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_173630.4(RTTN):c.4303-30_4303-11delTTTTTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 486,862 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000029 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0016 ( 1 hom. )

Consequence

RTTN
NM_173630.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.23

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

microcephalic primordial dwarfism due to RTTN deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
bilateral generalized polymicrogyria
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

RTTN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTTN	NM_173630.4 link	c.4303-30_4303-11delTTTTTTTTTTTTTTTTTTTT		intron_variant	Intron 31 of 48	ENST00000640769.2	NP_775901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTTN	ENST00000640769.2 link	c.4303-30_4303-11delTTTTTTTTTTTTTTTTTTTT		intron_variant	Intron 31 of 48	2	NM_173630.4	ENSP00000491507.1

Frequencies

GnomAD3 genomes

AF:

0.0000293

AC:

AN:

68178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000136

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00161

AC:

672

AN:

418684

Hom.:

AF XY:

0.00163

AC XY:

369

AN XY:

225692

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00145

AC:

AN:

6918

American (AMR)

AF:

0.00197

AC:

AN:

17732

Ashkenazi Jewish (ASJ)

AF:

0.00128

AC:

AN:

11688

East Asian (EAS)

AF:

0.00299

AC:

AN:

26402

South Asian (SAS)

AF:

0.00164

AC:

AN:

37114

European-Finnish (FIN)

AF:

0.00138

AC:

AN:

29636

Middle Eastern (MID)

AF:

0.00268

AC:

AN:

1490

European-Non Finnish (NFE)

AF:

0.00145

AC:

388

AN:

267504

Other (OTH)

AF:

0.00193

AC:

AN:

20200

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.283

Heterozygous variant carriers

120

181

241

301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000293

AC:

AN:

68178

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

30196

show subpopulations

African (AFR)

AF:

0.000136

AC:

AN:

14748

American (AMR)

AF:

0.00

AC:

AN:

5454

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2146

East Asian (EAS)

AF:

0.00

AC:

AN:

2162

South Asian (SAS)

AF:

0.00

AC:

AN:

1518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1152

Middle Eastern (MID)

AF:

0.00

AC:

AN:

108

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

39470

Other (OTH)

AF:

0.00

AC:

AN:

836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.2

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

18-70086694-TAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over