CFAP298 p.Ala130Ala

Variant names:

• chr21-32604268-C-C
• NM_021254.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr21-32604269--
• chr21-32604269-G-A
• chr21-32604269-G-T
• chr21-32604269-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021254.4(CFAP298):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP298 NM_021254.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719
• Publications: 0 publications found

Genes affected

CFAP298 (HGNC:1301): (cilia and flagella associated protein 298) This gene encodes a protein that plays a critical role in dynein arm assembly and motile cilia function. Mutations in this gene result in primary ciliary dyskinesia. Naturally occuring readthrough transcription occurs from this locus to the downstream t-complex 10 like (TCP10L) gene. [provided by RefSeq, Apr 2017]

CFAP298-TCP10L (HGNC:54636): (CFAP298-TCP10L readthrough) This locus represents naturally occurring readthrough transcription between the neighboring chromosome 21 open reading frame 59 (C21orf59) and TCP10L (t-complex 10 like) genes on chromosome 21. Readthrough transcripts may encode a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021254.4. 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
	CFAP298	NM_021254.4	MANE Select	c.		exon_region	Exon 4 of 7	NP_067077.1	P57076
	CFAP298-TCP10L	NM_001350338.2		c.		exon_region	Exon 4 of 8	NP_001337267.1	A0A669KAY3
	CFAP298	NM_001350337.2		c.		exon_region	Exon 4 of 6	NP_001337266.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP298	ENST00000290155.8	TSL:1 MANE Select	c.		exon_region	Exon 4 of 7	ENSP00000290155.3	P57076
	CFAP298-TCP10L	ENST00000673807.1		c.		exon_region	Exon 4 of 8	ENSP00000501088.1	A0A669KAY3
	CFAP298	ENST00000382549.8	TSL:1	c.		exon_region	Exon 4 of 5	ENSP00000371989.4	D3DSE6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.72

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: chr21-33976578;