NM_020800.3:c.2224-10delT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_020800.3(IFT80):​c.2224-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 1,510,686 control chromosomes in the GnomAD database, including 528 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (115 hom., cov: 0)
  • Exomes 𝑓: 0.024 (413 hom.)
• Consequence: IFT80 NM_020800.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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 -16 ACMG points.

• BP6: Variant 3-160258644-GA-G is Benign according to our data. Variant chr3-160258644-GA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 215528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT80	NM_020800.3	MANE Select	c.2224-10delT		intron	N/A	NP_065851.1	Q9P2H3-1
	IFT80	NM_001190241.2		c.1813-10delT		intron	N/A	NP_001177170.1	Q9P2H3-2
	IFT80	NM_001190242.2		c.1813-10delT		intron	N/A	NP_001177171.1	Q9P2H3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT80	ENST00000326448.12	TSL:1 MANE Select	c.2224-10delT		intron	N/A	ENSP00000312778.7	Q9P2H3-1
	IFT80	ENST00000483465.5	TSL:1	c.1813-10delT		intron	N/A	ENSP00000418196.1	Q9P2H3-2
	TRIM59-IFT80	ENST00000483754.1	TSL:2	n.2737-10delT		intron	N/A	ENSP00000456272.1	H3BRJ5

Frequencies

GnomAD3 genomes AF: 0.0334 AC: 4948 AN: 147952 Hom.: 115 Cov.: 0

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.0117

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00772

Gnomad FIN AF: 0.0114

Gnomad MID AF: 0.0452

Gnomad NFE AF: 0.0243

Gnomad OTH AF: 0.0366

GnomAD2 exomes AF: 0.0282 AC: 5278 AN: 187270 AF XY: 0.0264

Gnomad AFR exome AF: 0.0798

Gnomad AMR exome AF: 0.0268

Gnomad ASJ exome AF: 0.0168

Gnomad EAS exome AF: 0.00122

Gnomad FIN exome AF: 0.0151

Gnomad NFE exome AF: 0.0320

Gnomad OTH exome AF: 0.0280

GnomAD4 exome AF: 0.0236 AC: 32168 AN: 1362642 Hom.: 413 Cov.: 32 AF XY: 0.0229 AC XY: 15541 AN XY: 677994

African (AFR) AF: 0.0732 AC: 2268 AN: 30998

American (AMR) AF: 0.0208 AC: 821 AN: 39550

Ashkenazi Jewish (ASJ) AF: 0.0139 AC: 335 AN: 24154

East Asian (EAS) AF: 0.000165 AC: 6 AN: 36298

South Asian (SAS) AF: 0.00916 AC: 730 AN: 79692

European-Finnish (FIN) AF: 0.0116 AC: 516 AN: 44498

Middle Eastern (MID) AF: 0.0264 AC: 140 AN: 5296

European-Non Finnish (NFE) AF: 0.0247 AC: 25869 AN: 1046030

Other (OTH) AF: 0.0264 AC: 1483 AN: 56126

GnomAD4 genome AF: 0.0335 AC: 4959 AN: 148044 Hom.: 115 Cov.: 0 AF XY: 0.0327 AC XY: 2354 AN XY: 72038

African (AFR) AF: 0.0657 AC: 2656 AN: 40414

American (AMR) AF: 0.0276 AC: 407 AN: 14754

Ashkenazi Jewish (ASJ) AF: 0.0117 AC: 40 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 5036

South Asian (SAS) AF: 0.00731 AC: 34 AN: 4654

European-Finnish (FIN) AF: 0.0114 AC: 111 AN: 9718

Middle Eastern (MID) AF: 0.0524 AC: 15 AN: 286

European-Non Finnish (NFE) AF: 0.0243 AC: 1622 AN: 66812

Other (OTH) AF: 0.0362 AC: 74 AN: 2046

Alfa AF: 0.0149 Hom.: 500

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Jeune thoracic dystrophy (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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

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

Other links and lift over

dbSNP: rs58665245; hg19: chr3-159976432; COSMIC: COSV58448887;