Genetic Variant NM_001031743.3:c.262G>T (chr6-87413879-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001031743.3(CFAP206):c.262G>T(p.Asp88Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000359 in 1,393,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D88N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

CFAP206
NM_001031743.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.16

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.757

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP206	NM_001031743.3 link	c.262G>T	p.Asp88Tyr	missense_variant	Exon 4 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.262G>T	p.Asp88Tyr	missense_variant	Exon 4 of 13	1	NM_001031743.3	ENSP00000358575.4		Q8IYR0
ENSG00000213204	ENST00000507897.5 link	n.262G>T		non_coding_transcript_exon_variant	Exon 4 of 16	2		ENSP00000426769.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000512

AC:

AN:

195188

AF XY:

0.00000933

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000359

AC:

AN:

1393862

Hom.:

Cov.:

AF XY:

0.00000578

AC XY:

AN XY:

692140

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29254

American (AMR)

AF:

0.00

AC:

AN:

29654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24400

East Asian (EAS)

AF:

0.00

AC:

AN:

35746

South Asian (SAS)

AF:

0.0000688

AC:

AN:

72626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5436

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1086466

Other (OTH)

AF:

0.00

AC:

AN:

57732

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

T;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.042

MetaRNN

Pathogenic

0.76

D;D

MetaSVM

Benign

-0.77

PhyloP100

6.2

PROVEAN

Pathogenic

-5.3

D;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.036

D;D

Polyphen

1.0

D;.

Vest4

0.89

MutPred

0.54

Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);

MVP

0.59

MPC

0.73

ClinPred

0.98

GERP RS

5.3

Varity_R

0.35

gMVP

0.79

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over