rs144099135

Positions:

chr3-160307663-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBS1BS2

The NM_020800.3(IFT80):c.1076C>T(p.Ser359Phe) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00809 in 1,445,354 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 90 hom. )

Consequence

IFT80
NM_020800.3 missense, splice_region

Scores

Splicing: ADA: 0.9923

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.50

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:

TRIM59-IFT80 (HGNC:):

TRIM59-IFT80 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

BP6

Variant 3-160307663-G-A is Benign according to our data. Variant chr3-160307663-G-A is described in ClinVar as [Benign]. Clinvar id is 193733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-160307663-G-A is described in Lovd as [Benign]. Variant chr3-160307663-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00764 (1163/152250) while in subpopulation AMR AF= 0.0243 (372/15280). AF 95% confidence interval is 0.0223. There are 9 homozygotes in gnomad4. There are 569 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFT80	NM_020800.3 linkuse as main transcript	c.1076C>T	p.Ser359Phe	missense_variant, splice_region_variant	10/20	ENST00000326448.12
TRIM59-IFT80	NR_148401.1 linkuse as main transcript	n.1784C>T		splice_region_variant, non_coding_transcript_exon_variant	8/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT80	ENST00000326448.12 linkuse as main transcript	c.1076C>T	p.Ser359Phe	missense_variant, splice_region_variant	10/20	1	NM_020800.3	P1	Q9P2H3-1

Frequencies

GnomAD3 genomes

AF:

0.00762

AC:

1159

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00381

Gnomad AMI

AF:

0.0451

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.00481

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00737

Gnomad OTH

AF:

0.00671

GnomAD3 exomes

AF:

0.0108

AC:

2703

AN:

250732

Hom.:

AF XY:

0.00914

AC XY:

1239

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.00425

Gnomad AMR exome

AF:

0.0436

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00136

Gnomad SAS exome

AF:

0.00431

Gnomad FIN exome

AF:

0.00505

Gnomad NFE exome

AF:

0.00709

Gnomad OTH exome

AF:

0.00914

GnomAD4 exome

AF:

0.00814

AC:

10527

AN:

1293104

Hom.:

Cov.:

AF XY:

0.00770

AC XY:

5024

AN XY:

652494

show subpopulations

Gnomad4 AFR exome

AF:

0.00272

Gnomad4 AMR exome

AF:

0.0424

Gnomad4 ASJ exome

AF:

0.000159

Gnomad4 EAS exome

AF:

0.00123

Gnomad4 SAS exome

AF:

0.00440

Gnomad4 FIN exome

AF:

0.00551

Gnomad4 NFE exome

AF:

0.00772

Gnomad4 OTH exome

AF:

0.00812

GnomAD4 genome

AF:

0.00764

AC:

1163

AN:

152250

Hom.:

Cov.:

AF XY:

0.00764

AC XY:

569

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00378

Gnomad4 AMR

AF:

0.0243

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.00481

Gnomad4 NFE

AF:

0.00737

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00668

Hom.:

Bravo

AF:

0.00929

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00767

AC:

ExAC

AF:

0.00964

AC:

1170

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00720

EpiControl

AF:

0.00610

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Asphyxiating thoracic dystrophy 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 07, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 21, 2014

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Apr 14, 2015

- -

Jeune thoracic dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Feb 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

D;.;.;.

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;.;D;D

MetaRNN

Benign

0.0087

T;T;T;T

MetaSVM

Uncertain

-0.029

MutationAssessor

Pathogenic

3.0

M;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-5.0

D;D;D;D

REVEL

Uncertain

0.45

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.73

MPC

0.65

ClinPred

0.040

GERP RS

5.1

Varity_R

0.47

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.75

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

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