Variant rs753617262 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_020800.3(IFT80):c.1126G>T(p.Val376Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IFT80
NM_020800.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.35

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:

IFT80 (HGNC:):

IFT80 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT80	NM_020800.3 linkuse as main transcript	c.1126G>T	p.Val376Phe	missense_variant	11/20	ENST00000326448.12	NP_065851.1	Q9P2H3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT80	ENST00000326448.12 linkuse as main transcript	c.1126G>T	p.Val376Phe	missense_variant	11/20	1	NM_020800.3	ENSP00000312778.7		Q9P2H3-1
ENSG00000248710	ENST00000483754.1 linkuse as main transcript	n.1639G>T		non_coding_transcript_exon_variant	9/19	2		ENSP00000456272.1		H3BRJ5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251150

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458746

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725896

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

D;.;.;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;.;D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.77

D;D;D;D

MetaSVM

Uncertain

0.41

MutationAssessor

Pathogenic

3.1

M;.;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-4.0

D;D;D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

0.99

D;.;.;.

Vest4

0.86

MutPred

0.37

Loss of sheet (P = 0.1158);.;.;.;

MVP

0.93

MPC

0.72

ClinPred

0.99

GERP RS

5.3

Varity_R

0.78

gMVP

0.76

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over