10-104194005-G-GA

Variant names:

• chr10-104194005-G-GA
• rs1554882484
• NM_025145.7:c.1302dupT

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_025145.7(CFAP43):​c.1302dupT​(p.Leu435SerfsTer26) 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
• Publications: 3 publications found

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]

CFAP43 Gene-Disease associations (from GenCC):

• spermatogenic failure 19

  Inheritance: AR Classification: DEFINITIVE, LIMITED Submitted by: ClinGen, Ambry Genetics
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• normal pressure hydrocephalus

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000294028 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 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 VariationId is 523148.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025145.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP43	NM_025145.7	MANE Select	c.1302dupT	p.Leu435SerfsTer26	frameshift	Exon 11 of 38	NP_079421.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP43	ENST00000357060.8	TSL:1 MANE Select	c.1302dupT	p.Leu435SerfsTer26	frameshift	Exon 11 of 38	ENSP00000349568.3
	CFAP43	ENST00000278064.7	TSL:1	c.1305dupT	p.Leu436SerfsTer26	frameshift	Exon 11 of 22	ENSP00000278064.3
	CFAP43	ENST00000369720.6	TSL:1	c.1305dupT	p.Leu436SerfsTer26	frameshift	Exon 11 of 11	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

May 02, 2018

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.58
Mutation Taster		=2/198	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs1554882484; hg19: chr10-105953763;