13-20574472-C-A

Variant names:

• chr13-20574472-C-A
• NM_006531.5:c.87C>A
• IFT88 p.Ile29Ile

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_006531.5(IFT88):​c.87C>A​(p.Ile29Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I29I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IFT88 NM_006531.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 0 publications found

Genes affected

IFT88 (HGNC:20606): (intraflagellar transport 88) This gene encodes a member of the tetratrico peptide repeat (TPR) family. The encoded protein is involved in cilium biogenesis. Mutations of a similar gene in mouse can cause polycystic kidney disease. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2017]

IFT88 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP7: Synonymous conserved (PhyloP=-1.08 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006531.5. 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
	IFT88	NM_006531.5	MANE Select	c.87C>A	p.Ile29Ile	synonymous	Exon 2 of 26	NP_006522.2
	IFT88	NM_001318493.2		c.114C>A	p.Ile38Ile	synonymous	Exon 3 of 27	NP_001305422.1	Q13099-1
	IFT88	NM_001353565.2		c.114C>A	p.Ile38Ile	synonymous	Exon 3 of 27	NP_001340494.1	Q13099-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT88	ENST00000351808.10	TSL:1 MANE Select	c.87C>A	p.Ile29Ile	synonymous	Exon 2 of 26	ENSP00000261632.5	Q13099-2
	IFT88	ENST00000319980.10	TSL:1	c.114C>A	p.Ile38Ile	synonymous	Exon 4 of 28	ENSP00000323580.6	Q13099-1
	IFT88	ENST00000894242.1		c.87C>A	p.Ile29Ile	synonymous	Exon 3 of 27	ENSP00000564301.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1419984 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 708682

African (AFR) AF: 0.00 AC: 0 AN: 32398

American (AMR) AF: 0.00 AC: 0 AN: 43898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25776

East Asian (EAS) AF: 0.00 AC: 0 AN: 39106

South Asian (SAS) AF: 0.00 AC: 0 AN: 83812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077324

Other (OTH) AF: 0.00 AC: 0 AN: 58842

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	0.0060
DANN	Benign	0.73
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr13-21148611;