rs10513991

chr18-70088587-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173630.4(RTTN):c.4144-440T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0716 in 152,254 control chromosomes in the GnomAD database, including 789 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.072 (789 hom., cov: 32)
• Consequence: RTTN NM_173630.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTTN	NM_173630.4	c.4144-440T>C		intron_variant		ENST00000640769.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTTN	ENST00000640769.2	c.4144-440T>C		intron_variant		2	NM_173630.4	P1

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10883 AN: 152136 Hom.: 787 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0578

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0318

Gnomad FIN AF: 0.0383

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0655

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0716 AC: 10898 AN: 152254 Hom.: 789 Cov.: 32 AF XY: 0.0696 AC XY: 5181 AN XY: 74450

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.0578

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0325

Gnomad4 FIN AF: 0.0383

Gnomad4 NFE AF: 0.0259

Gnomad4 OTH AF: 0.0648

Alfa AF: 0.0451 Hom.: 66

Bravo AF: 0.0791

Asia WGS AF: 0.0260 AC: 91 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	8.5
Dann	Benign	0.61

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

LitVar

Other links and lift over

dbSNP: rs10513991; hg19: chr18-67755823;