rs750840329

Variant names:

• chr6-87418370-C-A
• rs750840329
• NM_001031743.3:c.794C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-87418370-C-A
• chr6-87418370-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001031743.3(CFAP206):​c.794C>A​(p.Ala265Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. A265V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CFAP206 NM_001031743.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.44
• Publications: 3 publications found

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]

ENSG00000213204 (HGNC:):

ACMG classification

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, 0.81

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031743.3. 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
	CFAP206	NM_001031743.3	MANE Select	c.794C>A	p.Ala265Glu	missense	Exon 7 of 13	NP_001026913.1	Q8IYR0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP206	ENST00000369562.9	TSL:1 MANE Select	c.794C>A	p.Ala265Glu	missense	Exon 7 of 13	ENSP00000358575.4	Q8IYR0
	ENSG00000213204	ENST00000507897.5	TSL:2	n.794C>A		non_coding_transcript_exon	Exon 7 of 16	ENSP00000426769.1
	CFAP206	ENST00000906987.1		c.794C>A	p.Ala265Glu	missense	Exon 7 of 13	ENSP00000577046.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.98	T
PhyloP100		3.4
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.26
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.83
MutPred		0.66		Loss of helix (P = 0.0795)
MVP		0.27
MPC		0.41
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.46
gMVP		0.78
Mutation Taster		=57/43	polymorphism

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: rs750840329; hg19: chr6-88128088;