Genetic Variant CFAP206:p.Arg234Trp (chr6-87418276-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001031743.3(CFAP206):c.700C>T(p.Arg234Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000756 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R234Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

CFAP206
NM_001031743.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.02

Variant links:

Genes affected

CFAP206 (HGNC:21405): (cilia and flagella associated protein 206) Predicted to be involved in regulation of cilium beat frequency; regulation of flagellated sperm motility; and sperm axoneme assembly. Predicted to be located in motile cilium. Predicted to be part of radial spoke. Predicted to be active in axoneme and ciliary basal body. Predicted to colocalize with A axonemal microtubule. [provided by Alliance of Genome Resources, Apr 2022]

CFAP206 links:

ENSG00000213204 (HGNC:):

ENSG00000213204 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07283887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP206	NM_001031743.3 link	c.700C>T	p.Arg234Trp	missense_variant	Exon 7 of 13	ENST00000369562.9	NP_001026913.1	Q8IYR0Q8N771

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP206	ENST00000369562.9 link	c.700C>T	p.Arg234Trp	missense_variant	Exon 7 of 13	1	NM_001031743.3	ENSP00000358575.4		Q8IYR0
ENSG00000213204	ENST00000507897.5 link	n.700C>T		non_coding_transcript_exon_variant	Exon 7 of 16	2		ENSP00000426769.1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000942

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000288

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:

0.000107

AC:

AN:

251482

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000547

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000536

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000276

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000940

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000288

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

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.000291

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.700C>T (p.R234W) alteration is located in exon 7 (coding exon 6) of the CFAP206 gene. This alteration results from a C to T substitution at nucleotide position 700, causing the arginine (R) at amino acid position 234 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.073

T;T

MetaSVM

Benign

-1.1

PROVEAN

Uncertain

-2.7

D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.024

D;D

Polyphen

1.0

D;.

Vest4

0.37

MVP

0.50

MPC

0.53

ClinPred

0.13

GERP RS

5.2

Varity_R

0.24

gMVP

0.38

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