21-44333058-CGG-TAA

Variant names:

• chr21-44333058-CGG-TAA
• NM_004928.3:c.346_348delCCGinsTTA
• CFAP410 p.Pro116Leu

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PS1_Very_Strong

The NM_004928.3(CFAP410):​c.346_348delCCGinsTTA​(p.Pro116Leu) variant causes a missense 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 MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar. Synonymous variant affecting the same amino acid position (i.e. P116P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CFAP410 NM_004928.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.30
• Publications: 0 publications found

Genes affected

CFAP410 (HGNC:1260): (cilia and flagella associated protein 410) Four alternatively spliced transcript variants encoding four different isoforms have been found for this nuclear gene. All isoforms contain leucine-rich repeats. Three of these isoforms are mitochondrial proteins and one of them lacks the target peptide, so is not located in mitochondrion. This gene is down-regulated in Down syndrome (DS) brain, which may represent mitochondrial dysfunction in DS patients. [provided by RefSeq, Sep 2012]

CFAP410 Gene-Disease associations (from GenCC):

• axial spondylometaphyseal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• amyotrophic lateral sclerosis

  Inheritance: AD, SD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000184441 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PS1: Transcript NM_004928.3 (CFAP410) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004928.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP410	NM_004928.3	MANE Select	c.346_348delCCGinsTTA	p.Pro116Leu	missense	N/A	NP_004919.1	O43822-1
	CFAP410	NM_001271441.2		c.346_348delCCGinsTTA	p.Pro116Leu	missense	N/A	NP_001258370.1	O43822-4
	CFAP410	NM_001271440.2		c.346_348delCCGinsTTA	p.Pro116Leu	missense	N/A	NP_001258369.1	O43822-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP410	ENST00000339818.9	TSL:1 MANE Select	c.346_348delCCGinsTTA	p.Pro116Leu	missense	N/A	ENSP00000344566.4	O43822-1
	CFAP410	ENST00000397956.7	TSL:1	c.346_348delCCGinsTTA	p.Pro116Leu	missense	N/A	ENSP00000381047.3	O43822-4
	CFAP410	ENST00000325223.7	TSL:1	c.346_348delCCGinsTTA	p.Pro116Leu	missense	N/A	ENSP00000317302.7	O43822-3

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-45752941;