3-160258644-GAAAA-GAAAAA

Variant names:

• chr3-160258644-G-GA
• rs58665245
• NM_020800.3:c.2224-10dupT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_020800.3(IFT80):​c.2224-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,479,792 control chromosomes in the GnomAD database, including 31,386 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.32 (7630 hom., cov: 0)
  • Exomes 𝑓: 0.27 (23756 hom.)
• Consequence: IFT80 NM_020800.3 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• 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: Benign. The variant received -9 ACMG points.

• BP6: Variant 3-160258644-G-GA is Benign according to our data. Variant chr3-160258644-G-GA is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 215529.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT80	NM_020800.3	c.2224-10dupT		intron_variant	Intron 19 of 19	ENST00000326448.12	NP_065851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT80	ENST00000326448.12	c.2224-10_2224-9insT		intron_variant	Intron 19 of 19	1	NM_020800.3	ENSP00000312778.7
TRIM59-IFT80	ENST00000483754.1	n.2737-10_2737-9insT		intron_variant	Intron 17 of 18	2		ENSP00000456272.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 46691 AN: 147816 Hom.: 7620 Cov.: 0

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.284

GnomAD2 exomes AF: 0.293 AC: 54812 AN: 187270 AF XY: 0.296

Gnomad AFR exome AF: 0.324

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.224

Gnomad FIN exome AF: 0.418

Gnomad NFE exome AF: 0.313

Gnomad OTH exome AF: 0.304

GnomAD4 exome AF: 0.274 AC: 365043 AN: 1331884 Hom.: 23756 Cov.: 32 AF XY: 0.273 AC XY: 181191 AN XY: 662730

African (AFR) AF: 0.327 AC: 9941 AN: 30418

American (AMR) AF: 0.153 AC: 5905 AN: 38526

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 8176 AN: 23666

East Asian (EAS) AF: 0.170 AC: 5939 AN: 34868

South Asian (SAS) AF: 0.218 AC: 16942 AN: 77732

European-Finnish (FIN) AF: 0.377 AC: 16573 AN: 43906

Middle Eastern (MID) AF: 0.296 AC: 1545 AN: 5224

European-Non Finnish (NFE) AF: 0.278 AC: 284746 AN: 1022804

Other (OTH) AF: 0.279 AC: 15276 AN: 54740

GnomAD4 genome AF: 0.316 AC: 46732 AN: 147908 Hom.: 7630 Cov.: 0 AF XY: 0.320 AC XY: 23006 AN XY: 71966

African (AFR) AF: 0.346 AC: 13982 AN: 40360

American (AMR) AF: 0.202 AC: 2977 AN: 14746

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1270 AN: 3426

East Asian (EAS) AF: 0.179 AC: 899 AN: 5032

South Asian (SAS) AF: 0.232 AC: 1080 AN: 4654

European-Finnish (FIN) AF: 0.480 AC: 4648 AN: 9690

Middle Eastern (MID) AF: 0.313 AC: 89 AN: 284

European-Non Finnish (NFE) AF: 0.311 AC: 20740 AN: 66776

Other (OTH) AF: 0.291 AC: 596 AN: 2046

Alfa AF: 0.208 Hom.: 500

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Jeune thoracic dystrophy Uncertain:1 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Oct 26, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Computational scores

Source: dbNSFP v4.3

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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs58665245; hg19: chr3-159976432;