chr11-102058896-CA-C

Variant names:

• chr11-102058896-CA-C
• rs1253909401
• NM_032930.3:c.212delA

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_032930.3(CFAP300):​c.212delA​(p.Asn71MetfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000505 in 1,584,130 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: CFAP300 NM_032930.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

Genes affected

CFAP300 (HGNC:28188): (cilia and flagella associated protein 300) Predicted to be located in cytoplasm and motile cilium. Implicated in primary ciliary dyskinesia 38. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 10 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP300	NM_032930.3	c.212delA	p.Asn71MetfsTer6	frameshift_variant	Exon 3 of 7	ENST00000434758.7	NP_116319.2
CFAP300	NM_001363505.2	c.212delA	p.Asn71MetfsTer6	frameshift_variant	Exon 3 of 6		NP_001350434.1
CFAP300	NM_001195005.2	c.212delA	p.Asn71MetfsTer6	frameshift_variant	Exon 3 of 4		NP_001181934.1
CFAP300	XM_005271713.5	c.212delA	p.Asn71MetfsTer6	frameshift_variant	Exon 3 of 6		XP_005271770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP300	ENST00000434758.7	c.212delA	p.Asn71MetfsTer6	frameshift_variant	Exon 3 of 7	2	NM_032930.3	ENSP00000414390.2
CFAP300	ENST00000534360.1	c.212delA	p.Asn71MetfsTer6	frameshift_variant	Exon 3 of 4	1		ENSP00000435482.1
CFAP300	ENST00000530659.1	n.449delA		non_coding_transcript_exon_variant	Exon 2 of 6	1
CFAP300	ENST00000526781.5	c.212delA	p.Asn71MetfsTer6	frameshift_variant	Exon 3 of 6	3		ENSP00000433074.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151878 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000422 AC: 1 AN: 236772 Hom.: 0 AF XY: 0.00000780 AC XY: 1 AN XY: 128206

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000905

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000489 AC: 7 AN: 1432252 Hom.: 0 Cov.: 27 AF XY: 0.00000281 AC XY: 2 AN XY: 712200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000637

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151878 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74166

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1253909401; hg19: chr11-101929627;