18-70086694-TAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAA

Position:

• chr18-70086694-TAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_173630.4(RTTN):​c.4303-23_4303-11delTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0076 in 417,648 control chromosomes in the GnomAD database, including 44 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.024 (36 hom., cov: 0)
  • Exomes 𝑓: 0.0076 (44 hom.)
  • Failed GnomAD Quality Control
• 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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0076 (3173/417648) while in subpopulation AFR AF= 0.0273 (188/6878). AF 95% confidence interval is 0.0241. There are 44 homozygotes in gnomad4_exome. There are 1577 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTTN	NM_173630.4	c.4303-23_4303-11delTTTTTTTTTTTTT		intron_variant		ENST00000640769.2	NP_775901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTTN	ENST00000640769.2	c.4303-23_4303-11delTTTTTTTTTTTTT		intron_variant		2	NM_173630.4	ENSP00000491507.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1615 AN: 68218 Hom.: 36 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.00342

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.0116

Gnomad EAS AF: 0.00185

Gnomad SAS AF: 0.00461

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.00926

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0239

GnomAD4 exome AF: 0.00760 AC: 3173 AN: 417648 Hom.: 44 AF XY: 0.00700 AC XY: 1577 AN XY: 225140

Gnomad4 AFR exome AF: 0.0273

Gnomad4 AMR exome AF: 0.00640

Gnomad4 ASJ exome AF: 0.00711

Gnomad4 EAS exome AF: 0.00322

Gnomad4 SAS exome AF: 0.00261

Gnomad4 FIN exome AF: 0.0112

Gnomad4 NFE exome AF: 0.00769

Gnomad4 OTH exome AF: 0.0104

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0237 AC: 1615 AN: 68246 Hom.: 36 Cov.: 0 AF XY: 0.0227 AC XY: 687 AN XY: 30238

Gnomad4 AFR AF: 0.0454

Gnomad4 AMR AF: 0.0203

Gnomad4 ASJ AF: 0.0116

Gnomad4 EAS AF: 0.00185

Gnomad4 SAS AF: 0.00464

Gnomad4 FIN AF: 0.0372

Gnomad4 NFE AF: 0.0185

Gnomad4 OTH AF: 0.0236

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;