chr3-160258644-G-GAAA

Variant names:

• chr3-160258644-G-GAAA
• rs58665245
• NM_020800.3:c.2224-12_2224-10dupTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020800.3(IFT80):​c.2224-12_2224-10dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000732 in 1,366,092 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: not found (cov: 0)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: IFT80 NM_020800.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• Publications: 0 publications found

Genes affected

IFT80 (HGNC:29262): (intraflagellar transport 80) The protein encoded by this gene is part of the intraflagellar transport complex B and is necessary for the function of motile and sensory cilia. Defects in this gene are a cause of asphyxiating thoracic dystrophy 2 (ATD2). Three transcript variants encoding two different isoforms have been found for this gene.[provided by RefSeq, Jun 2010]

TRIM59-IFT80 (HGNC:56756): (TRIM59-IFT80 readthrough (NMD candidate)) This locus represents naturally occurring readthrough transcription between the neighboring TRIM59 (tripartite motif containing 59) and IFT80 (intraflagellar transport 80) genes on chromosome 3. The readthrough transcript is unlikely to produce a protein product. [provided by RefSeq, Jun 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020800.3. 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
	IFT80	NM_020800.3	MANE Select	c.2224-12_2224-10dupTTT		intron	N/A	NP_065851.1
	IFT80	NM_001190241.2		c.1813-12_1813-10dupTTT		intron	N/A	NP_001177170.1
	IFT80	NM_001190242.2		c.1813-12_1813-10dupTTT		intron	N/A	NP_001177171.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT80	ENST00000326448.12	TSL:1 MANE Select	c.2224-10_2224-9insTTT		intron	N/A	ENSP00000312778.7
	IFT80	ENST00000483465.5	TSL:1	c.1813-10_1813-9insTTT		intron	N/A	ENSP00000418196.1
	TRIM59-IFT80	ENST00000483754.1	TSL:2	n.2737-10_2737-9insTTT		intron	N/A	ENSP00000456272.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 7.32e-7 AC: 1 AN: 1366092 Hom.: 0 Cov.: 32 AF XY: 0.00000147 AC XY: 1 AN XY: 679744

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31042

American (AMR) AF: 0.00 AC: 0 AN: 39808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24208

East Asian (EAS) AF: 0.00 AC: 0 AN: 36468

South Asian (SAS) AF: 0.00 AC: 0 AN: 80020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5318

European-Non Finnish (NFE) AF: 9.54e-7 AC: 1 AN: 1048310

Other (OTH) AF: 0.00 AC: 0 AN: 56258

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs58665245; hg19: chr3-159976432;