3-160258644-GAAAA-GAAAAAA

Variant names:

• chr3-160258644-G-GAA
• rs58665245
• NM_020800.3:c.2224-11_2224-10dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_020800.3(IFT80):​c.2224-11_2224-10dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,487,402 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0025 (0 hom.)
• Consequence: IFT80 NM_020800.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 0 ACMG points.

• PM2: Variant has high frequency in the AFR (0.00349) population. However there is too low homozygotes in high coverage region: (expected more than 1, got 0).
• BP6: Variant 3-160258644-G-GAA is Benign according to our data. Variant chr3-160258644-G-GAA is described in ClinVar as Benign. ClinVar VariationId is 1164287.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2224-11_2224-10dupTT		intron	N/A	NP_065851.1	Q9P2H3-1
	IFT80	NM_001190241.2		c.1813-11_1813-10dupTT		intron	N/A	NP_001177170.1	Q9P2H3-2
	IFT80	NM_001190242.2		c.1813-11_1813-10dupTT		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.2224-10_2224-9insTT		intron	N/A	ENSP00000312778.7	Q9P2H3-1
	IFT80	ENST00000483465.5	TSL:1	c.1813-10_1813-9insTT		intron	N/A	ENSP00000418196.1	Q9P2H3-2
	TRIM59-IFT80	ENST00000483754.1	TSL:2	n.2737-10_2737-9insTT		intron	N/A	ENSP00000456272.1	H3BRJ5

Frequencies

GnomAD3 genomes AF: 0.000196 AC: 29 AN: 147966 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000136

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000412

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000224

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00141 AC: 264 AN: 187270 AF XY: 0.00142

Gnomad AFR exome AF: 0.00141

Gnomad AMR exome AF: 0.000335

Gnomad ASJ exome AF: 0.00101

Gnomad EAS exome AF: 0.000457

Gnomad FIN exome AF: 0.00479

Gnomad NFE exome AF: 0.00145

Gnomad OTH exome AF: 0.00129

GnomAD4 exome AF: 0.00254 AC: 3402 AN: 1339344 Hom.: 0 Cov.: 32 AF XY: 0.00236 AC XY: 1575 AN XY: 666492

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

African (AFR) AF: 0.00407 AC: 123 AN: 30204

American (AMR) AF: 0.000708 AC: 28 AN: 39556

Ashkenazi Jewish (ASJ) AF: 0.00420 AC: 98 AN: 23310

East Asian (EAS) AF: 0.000496 AC: 18 AN: 36272

South Asian (SAS) AF: 0.000875 AC: 69 AN: 78842

European-Finnish (FIN) AF: 0.00590 AC: 254 AN: 43044

Middle Eastern (MID) AF: 0.00249 AC: 13 AN: 5220

European-Non Finnish (NFE) AF: 0.00258 AC: 2653 AN: 1027840

Other (OTH) AF: 0.00265 AC: 146 AN: 55056

⚠️ 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 AF: 0.000196 AC: 29 AN: 148058 Hom.: 0 Cov.: 0 AF XY: 0.000167 AC XY: 12 AN XY: 72048

African (AFR) AF: 0.000198 AC: 8 AN: 40424

American (AMR) AF: 0.000136 AC: 2 AN: 14756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4654

European-Finnish (FIN) AF: 0.000412 AC: 4 AN: 9716

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000224 AC: 15 AN: 66816

Other (OTH) AF: 0.00 AC: 0 AN: 2046

Alfa AF: 0.00722 Hom.: 500

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Jeune thoracic dystrophy (1)

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;