rs2304378

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_173630.4(RTTN):c.6144A>G(p.Val2048Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,612,234 control chromosomes in the GnomAD database, including 32,809 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2385 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30424 hom. )

Consequence

RTTN
NM_173630.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.268

Publications

12 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: Orphanet, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen
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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 18-70020624-T-C is Benign according to our data. Variant chr18-70020624-T-C is described in ClinVar as Benign. ClinVar VariationId is 130191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.268 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173630.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTTN	NM_173630.4	MANE Select	c.6144A>G	p.Val2048Val	synonymous	Exon 45 of 49	NP_775901.3
	RTTN	NM_001318520.2		c.3408A>G	p.Val1136Val	synonymous	Exon 44 of 48	NP_001305449.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RTTN	ENST00000640769.2	TSL:2 MANE Select	c.6144A>G	p.Val2048Val	synonymous	Exon 45 of 49	ENSP00000491507.1	Q86VV8-1
RTTN	ENST00000581161.5	TSL:1	n.*4458A>G		non_coding_transcript_exon	Exon 44 of 48	ENSP00000462926.1	J3KTD2
RTTN	ENST00000583043.5	TSL:1	n.*3415A>G		non_coding_transcript_exon	Exon 39 of 43	ENSP00000462733.1	J3KT00

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25642

AN:

152118

Hom.:

2389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0867

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.213

GnomAD2 exomes

AF:

0.191

AC:

47546

AN:

248918

AF XY:

0.200

show subpopulations

Gnomad AFR exome

AF:

0.0797

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.256

Gnomad EAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.201

AC:

292984

AN:

1459998

Hom.:

30424

Cov.:

AF XY:

0.203

AC XY:

147590

AN XY:

726224

show subpopulations

African (AFR)

AF:

0.0906

AC:

3029

AN:

33434

American (AMR)

AF:

0.116

AC:

5190

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

6673

AN:

26086

East Asian (EAS)

AF:

0.176

AC:

6985

AN:

39674

South Asian (SAS)

AF:

0.226

AC:

19446

AN:

86140

European-Finnish (FIN)

AF:

0.191

AC:

10222

AN:

53390

Middle Eastern (MID)

AF:

0.406

AC:

2339

AN:

5764

European-Non Finnish (NFE)

AF:

0.204

AC:

226685

AN:

1110508

Other (OTH)

AF:

0.206

AC:

12415

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

11260

22521

33781

45042

56302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7766

15532

23298

31064

38830

<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:

0.168

AC:

25629

AN:

152236

Hom.:

2385

Cov.:

AF XY:

0.169

AC XY:

12564

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0866

AC:

3597

AN:

41552

American (AMR)

AF:

0.155

AC:

2373

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

855

AN:

3472

East Asian (EAS)

AF:

0.180

AC:

932

AN:

5184

South Asian (SAS)

AF:

0.215

AC:

1037

AN:

4820

European-Finnish (FIN)

AF:

0.190

AC:

2016

AN:

10596

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14047

AN:

68004

Other (OTH)

AF:

0.211

AC:

445

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1096

2192

3289

4385

5481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.197

Hom.:

3976

Bravo

AF:

0.162

Asia WGS

AF:

0.171

AC:

599

AN:

3478

EpiCase

AF:

0.236

EpiControl

AF:

0.232

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Microcephalic primordial dwarfism due to RTTN deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

3.4

(source)

DANN

Benign

0.77

PhyloP100

0.27

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over