3-160366130-C-T

Position:

chr3-160366130-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020800.3(IFT80):c.462G>A(p.Ala154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,610,788 control chromosomes in the GnomAD database, including 404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A154A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.023 ( 58 hom., cov: 32)

Exomes 𝑓: 0.019 ( 346 hom. )

Consequence

IFT80
NM_020800.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.08

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 3-160366130-C-T is Benign according to our data. Variant chr3-160366130-C-T is described in ClinVar as [Benign]. Clinvar id is 343980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-160366130-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.08 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0229 (3457/151018) while in subpopulation AFR AF= 0.0363 (1492/41114). AF 95% confidence interval is 0.0348. There are 58 homozygotes in gnomad4. There are 1652 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFT80	NM_020800.3 linkuse as main transcript	c.462G>A	p.Ala154=	synonymous_variant	6/20	ENST00000326448.12
TRIM59-IFT80	NR_148401.1 linkuse as main transcript	n.1170G>A		non_coding_transcript_exon_variant	4/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT80	ENST00000326448.12 linkuse as main transcript	c.462G>A	p.Ala154=	synonymous_variant	6/20	1	NM_020800.3	P1	Q9P2H3-1

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3452

AN:

150902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0364

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0228

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00501

Gnomad FIN

AF:

0.00367

Gnomad MID

AF:

0.0192

Gnomad NFE

AF:

0.0203

Gnomad OTH

AF:

0.0214

GnomAD3 exomes

AF:

0.0165

AC:

4149

AN:

250950

Hom.:

AF XY:

0.0161

AC XY:

2177

AN XY:

135614

show subpopulations

Gnomad AFR exome

AF:

0.0403

Gnomad AMR exome

AF:

0.0106

Gnomad ASJ exome

AF:

0.0389

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00660

Gnomad FIN exome

AF:

0.00481

Gnomad NFE exome

AF:

0.0203

Gnomad OTH exome

AF:

0.0207

GnomAD4 exome

AF:

0.0191

AC:

27847

AN:

1459770

Hom.:

346

Cov.:

AF XY:

0.0189

AC XY:

13710

AN XY:

726280

show subpopulations

Gnomad4 AFR exome

AF:

0.0372

Gnomad4 AMR exome

AF:

0.0121

Gnomad4 ASJ exome

AF:

0.0365

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00713

Gnomad4 FIN exome

AF:

0.00564

Gnomad4 NFE exome

AF:

0.0205

Gnomad4 OTH exome

AF:

0.0196

GnomAD4 genome

AF:

0.0229

AC:

3457

AN:

151018

Hom.:

Cov.:

AF XY:

0.0224

AC XY:

1652

AN XY:

73696

show subpopulations

Gnomad4 AFR

AF:

0.0363

Gnomad4 AMR

AF:

0.0228

Gnomad4 ASJ

AF:

0.0337

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00543

Gnomad4 FIN

AF:

0.00367

Gnomad4 NFE

AF:

0.0203

Gnomad4 OTH

AF:

0.0212

Alfa

AF:

0.0212

Hom.:

Bravo

AF:

0.0258

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0223

EpiControl

AF:

0.0214

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	Oct 14, 2023	- -

Jeune thoracic dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

May 12, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.0

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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