Genetic Variant CFAP300:p.Gln52Lys (chr11-102047858-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032930.3(CFAP300):c.154C>A(p.Gln52Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CFAP300
NM_032930.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.967

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26839983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP300	NM_032930.3 link	c.154C>A	p.Gln52Lys	missense_variant	Exon 2 of 7	ENST00000434758.7	NP_116319.2	Q9BRQ4-1
CFAP300	NM_001363505.2 link	c.154C>A	p.Gln52Lys	missense_variant	Exon 2 of 6		NP_001350434.1
CFAP300	NM_001195005.2 link	c.154C>A	p.Gln52Lys	missense_variant	Exon 2 of 4		NP_001181934.1	Q7Z2V0
CFAP300	XM_005271713.5 link	c.154C>A	p.Gln52Lys	missense_variant	Exon 2 of 6		XP_005271770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CFAP300	ENST00000434758.7 link	c.154C>A	p.Gln52Lys	missense_variant	Exon 2 of 7	2	NM_032930.3	ENSP00000414390.2	Q9BRQ4-1
CFAP300	ENST00000534360.1 link	c.154C>A	p.Gln52Lys	missense_variant	Exon 2 of 4	1		ENSP00000435482.1	Q9BRQ4-3
CFAP300	ENST00000530659.1 link	n.391C>A		non_coding_transcript_exon_variant	Exon 1 of 6	1
CFAP300	ENST00000526781.5 link	c.154C>A	p.Gln52Lys	missense_variant	Exon 2 of 6	3		ENSP00000433074.1	E9PM77

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251426

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS 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:

0.00000137

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.034

T;.;.

Eigen

Benign

0.0021

Eigen_PC

Benign

0.026

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.0068

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.84

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.28

T;T;D

Polyphen

0.59

P;.;.

Vest4

0.44

MutPred

0.50

Gain of ubiquitination at Q52 (P = 0.0211);Gain of ubiquitination at Q52 (P = 0.0211);Gain of ubiquitination at Q52 (P = 0.0211);

MVP

0.20

MPC

0.044

ClinPred

0.63

GERP RS

2.3

Varity_R

0.12

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over