rs140202230

Variant names:

• chr3-160303973-T-A
• rs140202230
• NM_020800.3:c.1093A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-160303973-T-A
• chr3-160303973-T-C
• chr3-160303973-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM5

The NM_020800.3(IFT80):​c.1093A>T​(p.Thr365Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T365A) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFT80 NM_020800.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.45
• Publications: 1 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr3-160303973-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 406217.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT80	NM_020800.3	c.1093A>T	p.Thr365Ser	missense_variant	Exon 11 of 20	ENST00000326448.12	NP_065851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT80	ENST00000326448.12	c.1093A>T	p.Thr365Ser	missense_variant	Exon 11 of 20	1	NM_020800.3	ENSP00000312778.7
TRIM59-IFT80	ENST00000483754.1	n.1606A>T		non_coding_transcript_exon_variant	Exon 9 of 19	2		ENSP00000456272.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D;.;.;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;.;D;D
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.64	D;D;D;D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Uncertain	2.5	M;.;.;.
PhyloP100		7.5
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.3	D;D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.019	D;D;D;D
Sift4G	Benign	0.074	T;T;T;D
Polyphen		1.0	D;.;.;.
Vest4		0.58
MutPred		0.45		Loss of sheet (P = 0.0315);.;.;.;
MVP		0.97
MPC		0.62
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.34
gMVP		0.55
Mutation Taster		=42/58	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

Other links and lift over

dbSNP: rs140202230; hg19: chr3-160021761;