4-80963591-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP299	NM_152770.3	c.681C>G	p.His227Gln	missense_variant	6/6	ENST00000358105.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP299	ENST00000358105.8	c.681C>G	p.His227Gln	missense_variant	6/6	1	NM_152770.3	P1
CFAP299	ENST00000508675.1	c.732C>G	p.His244Gln	missense_variant	7/7	1
CFAP299	ENST00000508314.1	n.162C>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000406 AC: 1 AN: 246320 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133290

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 SAS 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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 2021

The c.732C>G (p.H244Q) alteration is located in exon 7 (coding exon 7) of the C4orf22 gene. This alteration results from a C to G substitution at nucleotide position 732, causing the histidine (H) at amino acid position 244 to be replaced by a glutamine (Q). 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	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;T;T
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Benign	-0.53	T
MutationTaster	Benign	0.95	N;N
PROVEAN	Pathogenic	-6.9	D;D;.
REVEL	Uncertain	0.44
Sift	Uncertain	0.0010	D;D;.
Sift4G	Uncertain	0.0020	D;D;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

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

Other links and lift over

dbSNP: rs766302699; hg19: chr4-81884745;