chr18-70086694-T-TAAAAAAAAA

Variant names:

• chr18-70086694-T-TAAAAAAAAA
• rs531741265
• NM_173630.4:c.4303-19_4303-11dupTTTTTTTTT

Variant summary

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

The NM_173630.4(RTTN):​c.4303-19_4303-11dupTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000044 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: RTTN NM_173630.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 0 publications found

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

ACMG classification

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

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTTN	NM_173630.4	MANE Select	c.4303-19_4303-11dupTTTTTTTTT		intron	N/A	NP_775901.3
	RTTN	NM_001318520.2		c.1567-19_1567-11dupTTTTTTTTT		intron	N/A	NP_001305449.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTTN	ENST00000640769.2	TSL:2 MANE Select	c.4303-11_4303-10insTTTTTTTTT		intron	N/A	ENSP00000491507.1
	RTTN	ENST00000581161.5	TSL:1	n.*2617-11_*2617-10insTTTTTTTTT		intron	N/A	ENSP00000462926.1
	RTTN	ENST00000583043.5	TSL:1	n.*1574-11_*1574-10insTTTTTTTTT		intron	N/A	ENSP00000462733.1

Frequencies

GnomAD3 genomes AF: 0.0000440 AC: 3 AN: 68178 Hom.: 0 Cov.: 0

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: 0.0000253

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000477 AC: 2 AN: 419612 Hom.: 0 Cov.: 0 AF XY: 0.00000884 AC XY: 2 AN XY: 226198

African (AFR) AF: 0.00 AC: 0 AN: 6930

American (AMR) AF: 0.00 AC: 0 AN: 17750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11714

East Asian (EAS) AF: 0.00 AC: 0 AN: 26534

South Asian (SAS) AF: 0.0000269 AC: 1 AN: 37166

European-Finnish (FIN) AF: 0.0000337 AC: 1 AN: 29676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1494

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 268102

Other (OTH) AF: 0.00 AC: 0 AN: 20246

GnomAD4 genome AF: 0.0000440 AC: 3 AN: 68178 Hom.: 0 Cov.: 0 AF XY: 0.0000994 AC XY: 3 AN XY: 30196

African (AFR) AF: 0.000136 AC: 2 AN: 14748

American (AMR) AF: 0.00 AC: 0 AN: 5454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2146

East Asian (EAS) AF: 0.00 AC: 0 AN: 2162

South Asian (SAS) AF: 0.00 AC: 0 AN: 1518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 108

European-Non Finnish (NFE) AF: 0.0000253 AC: 1 AN: 39470

Other (OTH) AF: 0.00 AC: 0 AN: 836

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0

Splicing

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

Other links and lift over

dbSNP: rs531741265; hg19: chr18-67753930;