4-80963591-C-G

Variant names:

• chr4-80963591-C-G
• rs766302699
• NM_152770.3:c.681C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152770.3(CFAP299):​c.681C>G​(p.His227Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP299 NM_152770.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.638
• Publications: 0 publications found

Genes affected

CFAP299 (HGNC:28554): (cilia and flagella associated protein 299) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152770.3. 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
	CFAP299	NM_152770.3	MANE Select	c.681C>G	p.His227Gln	missense	Exon 6 of 6	NP_689983.2	Q6V702-2
	CFAP299	NM_001206997.2		c.732C>G	p.His244Gln	missense	Exon 7 of 7	NP_001193926.1	Q6V702-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP299	ENST00000358105.8	TSL:1 MANE Select	c.681C>G	p.His227Gln	missense	Exon 6 of 6	ENSP00000350818.3	Q6V702-2
	CFAP299	ENST00000508675.1	TSL:1	c.732C>G	p.His244Gln	missense	Exon 7 of 7	ENSP00000425786.1	Q6V702-1
	CFAP299	ENST00000508314.1	TSL:3	n.162C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000406 AC: 1 AN: 246320 AF XY: 0.00

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: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	0.96
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.092
Eigen_PC	Benign	-0.075
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.53	T
PhyloP100		-0.64
PROVEAN	Pathogenic	-6.9	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.53		Gain of MoRF binding (P = 0.0759)
MVP		0.12
MPC		0.51
ClinPred		0.97	D
GERP RS		0.26
Varity_R		0.78
gMVP		0.80
Mutation Taster		=73/27	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: rs766302699; hg19: chr4-81884745;