Genetic Variant CFAP300:p.Ala45Val (chr11-102047838-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032930.3(CFAP300):c.134C>T(p.Ala45Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,614,080 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CFAP300
NM_032930.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.53

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008978814).

BP6

Variant 11-102047838-C-T is Benign according to our data. Variant chr11-102047838-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1681448.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP300	NM_032930.3 link	c.134C>T	p.Ala45Val	missense_variant	Exon 2 of 7	ENST00000434758.7	NP_116319.2	Q9BRQ4-1
CFAP300	NM_001363505.2 link	c.134C>T	p.Ala45Val	missense_variant	Exon 2 of 6		NP_001350434.1
CFAP300	NM_001195005.2 link	c.134C>T	p.Ala45Val	missense_variant	Exon 2 of 4		NP_001181934.1	Q7Z2V0
CFAP300	XM_005271713.5 link	c.134C>T	p.Ala45Val	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.134C>T	p.Ala45Val	missense_variant	Exon 2 of 7	2	NM_032930.3	ENSP00000414390.2	Q9BRQ4-1
CFAP300	ENST00000534360.1 link	c.134C>T	p.Ala45Val	missense_variant	Exon 2 of 4	1		ENSP00000435482.1	Q9BRQ4-3
CFAP300	ENST00000530659.1 link	n.371C>T		non_coding_transcript_exon_variant	Exon 1 of 6	1
CFAP300	ENST00000526781.5 link	c.134C>T	p.Ala45Val	missense_variant	Exon 2 of 6	3		ENSP00000433074.1	E9PM77

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000282

AC:

AN:

251438

Hom.:

AF XY:

0.000294

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00556

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000136

AC:

199

AN:

1461874

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

110

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00547

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000191

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000313

Hom.:

Bravo

AF:

0.000193

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000206

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

T;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.0090

T;T;T

MetaSVM

Benign

-0.96

PROVEAN

Benign

-0.53

N;N;N

REVEL

Benign

0.058

Sift

Benign

0.51

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.066

B;.;.

Vest4

0.34

MVP

0.20

MPC

0.036

ClinPred

0.052

GERP RS

3.5

Varity_R

0.099

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over