18-70086694-TAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAA

Position:

• chr18-70086694-TAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_173630.4(RTTN):​c.4303-29_4303-11delTTTTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 485,790 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000088 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0069 (0 hom.)
• Consequence: RTTN NM_173630.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0069 (2883/417586) while in subpopulation MID AF= 0.0114 (17/1488). AF 95% confidence interval is 0.00988. There are 0 homozygotes in gnomad4_exome. There are 1596 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTTN	NM_173630.4	c.4303-29_4303-11delTTTTTTTTTTTTTTTTTTT		intron_variant		ENST00000640769.2	NP_775901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTTN	ENST00000640769.2	c.4303-29_4303-11delTTTTTTTTTTTTTTTTTTT		intron_variant		2	NM_173630.4	ENSP00000491507.1

Frequencies

GnomAD3 genomes AF: 0.0000880 AC: 6 AN: 68176 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000271

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: 0.000868

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000253

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00225 AC: 205 AN: 90912 Hom.: 0 AF XY: 0.00213 AC XY: 111 AN XY: 52036

Gnomad AFR exome AF: 0.00321

Gnomad AMR exome AF: 0.00416

Gnomad ASJ exome AF: 0.000729

Gnomad EAS exome AF: 0.00561

Gnomad SAS exome AF: 0.00274

Gnomad FIN exome AF: 0.000205

Gnomad NFE exome AF: 0.00157

Gnomad OTH exome AF: 0.00405

GnomAD4 exome AF: 0.00690 AC: 2883 AN: 417586 Hom.: 0 AF XY: 0.00709 AC XY: 1596 AN XY: 225116

Gnomad4 AFR exome AF: 0.00493

Gnomad4 AMR exome AF: 0.00713

Gnomad4 ASJ exome AF: 0.00703

Gnomad4 EAS exome AF: 0.0109

Gnomad4 SAS exome AF: 0.00618

Gnomad4 FIN exome AF: 0.00569

Gnomad4 NFE exome AF: 0.00660

Gnomad4 OTH exome AF: 0.00887

GnomAD4 genome AF: 0.0000880 AC: 6 AN: 68204 Hom.: 0 Cov.: 0 AF XY: 0.0000662 AC XY: 2 AN XY: 30224

Gnomad4 AFR AF: 0.000271

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000868

Gnomad4 NFE AF: 0.0000253

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs531741265; hg19: chr18-67753930;