chr3-160257301-G-GTA

Position:

• chr3-160257301-G-GTA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020800.3(IFT80):​c.*1222_*1223dupTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000473 in 150,208 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IFT80 NM_020800.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.472

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]

ENSG00000248710 (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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT80	NM_020800.3	c.*1222_*1223dupTA		3_prime_UTR_variant	20/20	ENST00000326448.12	NP_065851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT80	ENST00000326448	c.*1222_*1223dupTA		3_prime_UTR_variant	20/20	1	NM_020800.3	ENSP00000312778.7
IFT80	ENST00000483465	c.*1222_*1223dupTA		3_prime_UTR_variant	19/19	1		ENSP00000418196.1
ENSG00000248710	ENST00000483754.1	n.*58+1164_*58+1165dupTA		intron_variant		2		ENSP00000456272.1

Frequencies

GnomAD3 genomes AF: 0.000486 AC: 73 AN: 150116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000635

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000732

Gnomad ASJ AF: 0.000580

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00126

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000341

Gnomad OTH AF: 0.00146

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.000473 AC: 71 AN: 150208 Hom.: 0 Cov.: 32 AF XY: 0.000518 AC XY: 38 AN XY: 73334

Gnomad4 AFR AF: 0.000658

Gnomad4 AMR AF: 0.000731

Gnomad4 ASJ AF: 0.000580

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00105

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000341

Gnomad4 OTH AF: 0.000963

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Jeune thoracic dystrophy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs150435844; hg19: chr3-159975089;