rs1554882484

Positions:

• chr10-104194005-G-GA

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_025145.7(CFAP43):​c.1302dupT​(p.Leu435fs) 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 (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP43 NM_025145.7 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.576

Genes affected

CFAP43 (HGNC:26684): (cilia and flagella associated protein 43) This gene encodes a member of the cilia- and flagella-associated protein family. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-104194005-G-GA is Pathogenic according to our data. Variant chr10-104194005-G-GA is described in ClinVar as [Pathogenic]. Clinvar id is 523148.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP43	NM_025145.7	c.1302dupT	p.Leu435fs	frameshift_variant	11/38	ENST00000357060.8	NP_079421.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP43	ENST00000357060.8	c.1302dupT	p.Leu435fs	frameshift_variant	11/38	1	NM_025145.7	ENSP00000349568.3
CFAP43	ENST00000278064.7	c.1305dupT	p.Leu436fs	frameshift_variant	11/22	1		ENSP00000278064.3
CFAP43	ENST00000369720.6	c.1305dupT	p.Leu436fs	frameshift_variant	11/11	1		ENSP00000358734.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spermatogenic failure 19 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1554882484; hg19: chr10-105953763;