9-132499429-G-A

Variant names:

• chr9-132499429-G-A
• rs750950057
• NM_001282957.2:c.353G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001282957.2(CFAP77):​c.353G>A​(p.Arg118Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: CFAP77 NM_001282957.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57

Genes affected

CFAP77 (HGNC:33776): (cilia and flagella associated protein 77) Predicted to be located in cilium. [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 rank	MANE	Protein	UniProt
CFAP77	NM_001282957.2	c.353G>A	p.Arg118Gln	missense_variant	Exon 3 of 6	ENST00000393216.3	NP_001269886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP77	ENST00000393216.3	c.353G>A	p.Arg118Gln	missense_variant	Exon 3 of 6	1	NM_001282957.2	ENSP00000376909.2
CFAP77	ENST00000343036.6	c.461G>A	p.Arg154Gln	missense_variant	Exon 4 of 7	2		ENSP00000343290.2
CFAP77	ENST00000393215.7	c.353G>A	p.Arg118Gln	missense_variant	Exon 3 of 4	5		ENSP00000376908.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251334 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135866

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461872 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.461G>A (p.R154Q) alteration is located in exon 4 (coding exon 4) of the CFAP77 gene. This alteration results from a G to A substitution at nucleotide position 461, causing the arginine (R) at amino acid position 154 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	Benign	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	.;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Benign	-0.97	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.20
Sift	Benign	0.068	T;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0, 1.0	.;D;D
Vest4		0.68
MutPred		0.53		.;Loss of MoRF binding (P = 0.0402);.;
MVP		0.30
MPC		0.49
ClinPred		0.89	D
GERP RS		4.3
Varity_R		0.20
gMVP		0.69

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: rs750950057; hg19: chr9-135374816; COSMIC: COSV58018663;