rs1555672928

chr18-50261062-ACCTGAATTGCTGGTCTAGCTTTTCAGCCACAAAATCCTGCCTCTCTTTTTCATTCTTCTCTTTTAGTAATTTAGTTTTCTCTCTCATCCTATCTTTTTTCTCCTCAATGGTTTCTTTCTTCAATTGCATTTCTGTAAAATACTCATTTTCTTCTAATGCTAAAAGCTCACGTAG-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PP3 PP5

The NM_145020.5(CFAP53):c.301_473+1del variant causes a splice donor, coding sequence change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (no stars).

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

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.11197411 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• 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/exons	MANE	UniProt
CFAP53	NM_145020.5	c.301_473+1del		splice_donor_variant, coding_sequence_variant	3/8	ENST00000398545.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP53	ENST00000398545.5	c.301_473+1del		splice_donor_variant, coding_sequence_variant	3/8	1	NM_145020.5	P1

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

Likely pathogenic, no assertion criteria provided

research

Department of Medical Biology, Academic Medical Center

Sep 01, 2015

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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: rs1555672928; hg19: chr18-47787432;