IFT80 p.His105Gln

Variant names:

• chr3-160377485-G-T
• ENST00000483465.5:c.-97C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-160377485-G-T
• chr3-160377485-G-C

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PS1 PM2 PP3_Strong

The NM_020800.3(IFT80):​c.315C>A​(p.His105Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFT80 NM_020800.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• 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: Pathogenic. The variant received 10 ACMG points.

• PS1: Transcript NM_020800.3 (IFT80) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.969

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.315C>A	p.His105Gln	missense	Exon 4 of 20	NP_065851.1	Q9P2H3-1
	IFT80	NM_001190241.2		c.-97C>A		5_prime_UTR_premature_start_codon_gain	Exon 5 of 21	NP_001177170.1	Q9P2H3-2
	IFT80	NM_001190242.2		c.-97C>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 19	NP_001177171.1	Q9P2H3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT80	ENST00000483465.5	TSL:1	c.-97C>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 19	ENSP00000418196.1	Q9P2H3-2
	IFT80	ENST00000326448.12	TSL:1 MANE Select	c.315C>A	p.His105Gln	missense	Exon 4 of 20	ENSP00000312778.7	Q9P2H3-1
	IFT80	ENST00000483465.5	TSL:1	c.-97C>A		5_prime_UTR	Exon 3 of 19	ENSP00000418196.1	Q9P2H3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Pathogenic	4.3	H
PhyloP100		0.30
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0050	D
Varity_R		0.38
gMVP		0.75
Mutation Taster		=13/87	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-160095273;