rs1555071691

chr11-102083171-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_032930.3(CFAP300):c.776A>G(p.His259Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000647 in 1,390,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: CFAP300 NM_032930.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.45

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.969
• PP5: Variant 11-102083171-A-G is Pathogenic according to our data. Variant chr11-102083171-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 549858.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-102083171-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP300	NM_032930.3	c.776A>G	p.His259Arg	missense_variant	7/7	ENST00000434758.7
CFAP300	NM_001363505.2	c.704A>G	p.His235Arg	missense_variant	6/6
CFAP300	XM_005271713.5	c.709A>G	p.Thr237Ala	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP300	ENST00000434758.7	c.776A>G	p.His259Arg	missense_variant	7/7	2	NM_032930.3	P1
CFAP300	ENST00000530659.1	n.1013A>G		non_coding_transcript_exon_variant	6/6	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000178 AC: 4 AN: 224174 Hom.: 0 AF XY: 0.0000163 AC XY: 2 AN XY: 122352

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: 0.000149

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000647 AC: 9 AN: 1390394 Hom.: 0 Cov.: 27 AF XY: 0.0000101 AC XY: 7 AN XY: 690646

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: 0.000123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Ciliary dyskinesia, primary, 38 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.42
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.21	D
MutationTaster	Benign	1.0	D
PROVEAN	Pathogenic	-6.4	D
REVEL	Pathogenic	0.77
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.85		Gain of solvent accessibility (P = 0.0584);
MVP		0.26
MPC		0.28
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.88
gMVP		0.73

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: rs1555071691; hg19: chr11-101953902;