NM_145020.5:c.301_473+1del

Variant names:

• chr18-50261062-ACCTGAATTGCTGGTCTAGCTTTTCAGCCACAAAATCCTGCCTCTCTTTTTCATTCTTCTCTTTTAGTAATTTAGTTTTCTCTCTCATCCTATCTTTTTTCTCCTCAATGGTTTCTTTCTTCAATTGCATTTCTGTAAAATACTCATTTTCTTCTAATGCTAAAAGCTCACGTAG-A
• rs1555672928
• NM_145020.5:c.301_473+1del

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_145020.5(CFAP53):​c.301_473+1del​(p.Leu101fs) variant causes a frameshift, splice donor, splice region, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 30)
• Consequence: CFAP53 NM_145020.5 frameshift, splice_donor, splice_region, intron
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.63
• Publications: 0 publications found

Genes affected

CFAP53 (HGNC:26530): (cilia and flagella associated protein 53) This gene belongs to the CFAP53 family. It was found to be differentially expressed by the ciliated cells of frog epidermis and in skin fibroblasts from human. Mutations in this gene are associated with visceral heterotaxy-6, which implicates this gene in determination of left-right asymmetric patterning. [provided by RefSeq, Aug 2015]

CFAP53 Gene-Disease associations (from GenCC):

• heterotaxy, visceral, 6, autosomal

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 18-50261062-ACCTGAATTGCTGGTCTAGCTTTTCAGCCACAAAATCCTGCCTCTCTTTTTCATTCTTCTCTTTTAGTAATTTAGTTTTCTCTCTCATCCTATCTTTTTTCTCCTCAATGGTTTCTTTCTTCAATTGCATTTCTGTAAAATACTCATTTTCTTCTAATGCTAAAAGCTCACGTAG-A is Pathogenic according to our data. Variant chr18-50261062-ACCTGAATTGCTGGTCTAGCTTTTCAGCCACAAAATCCTGCCTCTCTTTTTCATTCTTCTCTTTTAGTAATTTAGTTTTCTCTCTCATCCTATCTTTTTTCTCCTCAATGGTTTCTTTCTTCAATTGCATTTCTGTAAAATACTCATTTTCTTCTAATGCTAAAAGCTCACGTAG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 488411.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP53	NM_145020.5	c.301_473+1del	p.Leu101fs	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	Exon 3 of 8	ENST00000398545.5	NP_659457.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP53	ENST00000398545.5	c.301_473+1del	p.Leu101fs	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	Exon 3 of 8	1	NM_145020.5	ENSP00000381553.3

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Dextrocardia Pathogenic:1

Sep 01, 2015

Department of Medical Biology, Academic Medical Center

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.6

Splicing

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

Other links and lift over

dbSNP: rs1555672928; hg19: chr18-47787432;