3-160319837-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020800.3(IFT80):c.880G>A(p.Val294Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000497 in 1,612,956 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 4 hom. )

Consequence

IFT80
NM_020800.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.77

Variant links:

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]

IFT80 links:

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]

ENSG00000248710 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007196605).

BP6

Variant 3-160319837-C-T is Benign according to our data. Variant chr3-160319837-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 459284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00209 (317/151968) while in subpopulation AFR AF= 0.00639 (265/41494). AF 95% confidence interval is 0.00575. There are 1 homozygotes in gnomad4. There are 161 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT80	NM_020800.3 link	c.880G>A	p.Val294Ile	missense_variant	Exon 9 of 20	ENST00000326448.12	NP_065851.1	Q9P2H3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT80	ENST00000326448.12 link	c.880G>A	p.Val294Ile	missense_variant	Exon 9 of 20	1	NM_020800.3	ENSP00000312778.7		Q9P2H3-1
ENSG00000248710	ENST00000483754.1 link	n.1393G>A		non_coding_transcript_exon_variant	Exon 7 of 19	2		ENSP00000456272.1		H3BRJ5

Frequencies

GnomAD3 genomes

AF:

0.00207

AC:

314

AN:

151850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00633

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00119

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000737

AC:

185

AN:

250988

Hom.:

AF XY:

0.000612

AC XY:

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.00690

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.000335

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000331

AC:

484

AN:

1460988

Hom.:

Cov.:

AF XY:

0.000315

AC XY:

229

AN XY:

726790

show subpopulations

Gnomad4 AFR exome

AF:

0.00700

Gnomad4 AMR exome

AF:

0.000381

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000749

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.000613

GnomAD4 genome

AF:

0.00209

AC:

317

AN:

151968

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

161

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.00639

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000610

Hom.:

Bravo

AF:

0.00239

ESP6500AA

AF:

0.00726

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000799

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Asphyxiating thoracic dystrophy 2

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided

Benign:1

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

IFT80: BP4 -

Jeune thoracic dystrophy

Benign:1

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

IFT80-related disorder

Benign:1

May 06, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.052

T;.;.

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.82

T;.;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.0072

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.7

N;.;.

PrimateAI

Benign

0.47

PROVEAN

Benign

0.40

N;N;N

REVEL

Benign

0.067

Sift

Benign

0.76

T;T;T

Sift4G

Benign

0.85

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.16

MVP

0.23

MPC

0.12

ClinPred

0.017

GERP RS

4.7

Varity_R

0.035

gMVP

0.076

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over