rs137853115

Variant names:

• chr3-160377485-G-C
• rs137853115
• NM_020800.3:c.315C>G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_020800.3(IFT80):​c.315C>G​(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. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFT80 NM_020800.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.300

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]

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.969
• PP5: Variant 3-160377485-G-C is Pathogenic according to our data. Variant chr3-160377485-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 989.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT80	NM_020800.3	c.315C>G	p.His105Gln	missense_variant	Exon 4 of 20	ENST00000326448.12	NP_065851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT80	ENST00000326448.12	c.315C>G	p.His105Gln	missense_variant	Exon 4 of 20	1	NM_020800.3	ENSP00000312778.7
ENSG00000248710	ENST00000483754.1	n.953-11333C>G		intron_variant	Intron 3 of 18	2		ENSP00000456272.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Asphyxiating thoracic dystrophy 2 Pathogenic:1

Aug 01, 2009

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D;T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Uncertain	0.70	D
MutationAssessor	Pathogenic	4.3	H;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.6	D;D;D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0050	D;.;.
Polyphen		1.0	D;.;.
Vest4		0.98
MutPred		0.90		Gain of ubiquitination at K100 (P = 0.1204);Gain of ubiquitination at K100 (P = 0.1204);Gain of ubiquitination at K100 (P = 0.1204);
MVP		0.93
MPC		0.64
ClinPred		0.99	D
GERP RS		2.4
Varity_R		0.38
gMVP		0.75

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

Other links and lift over

dbSNP: rs137853115; hg19: chr3-160095273;