rs1555474009

Positions:

• chr16-1511093-A-AGTAG

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Moderate PM2 PP5_Moderate

The NM_014714.4(IFT140):​c.4239_4240insCTAC​(p.Tyr1414LeufsTer48) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IFT140 NM_014714.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.80

Genes affected

IFT140 (HGNC:29077): (intraflagellar transport 140) This gene encodes one of the subunits of the intraflagellar transport (IFT) complex A. Intraflagellar transport is involved in the genesis, resorption and signaling of primary cilia. The primary cilium is a microtubule-based sensory organelle at the surface of most quiescent mammalian cells, that receives signals from its environment, such as the flow of fluid, light or odors, and transduces those signals to the nucleus. Loss of the corresponding protein in mouse results in renal cystic disease. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0342 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-1511093-A-AGTAG is Pathogenic according to our data. Variant chr16-1511093-A-AGTAG is described in ClinVar as [Pathogenic]. Clinvar id is 523182.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT140	NM_014714.4	c.4239_4240insCTAC	p.Tyr1414LeufsTer48	frameshift_variant	31/31	ENST00000426508.7	NP_055529.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT140	ENST00000426508.7	c.4239_4240insCTAC	p.Tyr1414LeufsTer48	frameshift_variant	31/31	5	NM_014714.4	ENSP00000406012	P1
IFT140	ENST00000361339.9	c.1821_1822insCTAC	p.Tyr608LeufsTer48	frameshift_variant	13/13	1		ENSP00000354895
IFT140	ENST00000565298.5	n.4063_4064insCTAC		non_coding_transcript_exon_variant	19/19	2
IFT140	ENST00000397417.6	c.*2677_*2678insCTAC		3_prime_UTR_variant, NMD_transcript_variant	24/24	5		ENSP00000380562

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinal ciliopathy due to mutation in the retinitis pigmentosa-1 gene Pathogenic:1

Pathogenic, criteria provided, single submitter

research

Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University

Jan 01, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555474009; hg19: chr16-1561094;