NM_032930.3:c.776A>G

Variant names:

• chr11-102083171-A-G
• rs1555071691
• NM_032930.3:c.776A>G

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. 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
• Publications: 0 publications found

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]

CFAP300 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 38

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• 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 VariationId is 549858.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032930.3. 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
	CFAP300	NM_032930.3	MANE Select	c.776A>G	p.His259Arg	missense	Exon 7 of 7	NP_116319.2	Q9BRQ4-1
	CFAP300	NM_001441265.1		c.709A>G	p.Thr237Ala	missense	Exon 6 of 6	NP_001428194.1
	CFAP300	NM_001363505.2		c.704A>G	p.His235Arg	missense	Exon 6 of 6	NP_001350434.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP300	ENST00000434758.7	TSL:2 MANE Select	c.776A>G	p.His259Arg	missense	Exon 7 of 7	ENSP00000414390.2	Q9BRQ4-1
	CFAP300	ENST00000530659.1	TSL:1	n.1013A>G		non_coding_transcript_exon	Exon 6 of 6
	CFAP300	ENST00000879551.1		c.704A>G	p.His235Arg	missense	Exon 6 of 6	ENSP00000549610.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000178 AC: 4 AN: 224174 AF XY: 0.0000163

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 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

African (AFR) AF: 0.00 AC: 0 AN: 31082

American (AMR) AF: 0.00 AC: 0 AN: 38636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24518

East Asian (EAS) AF: 0.00 AC: 0 AN: 37066

South Asian (SAS) AF: 0.000123 AC: 9 AN: 73204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5530

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072800

Other (OTH) AF: 0.00 AC: 0 AN: 57032

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Ciliary dyskinesia, primary, 38 (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		7.4
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
Mutation Taster		=13/87	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs1555071691; hg19: chr11-101953902;