9-132499449-C-A

Variant names:

• chr9-132499449-C-A
• rs769398138
• NM_001282957.2:c.373C>A

Variant summary

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

The NM_001282957.2(CFAP77):​c.373C>A​(p.Arg125Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R125H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CFAP77 NM_001282957.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543
• Publications: 1 publications found

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

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_001282957.2. 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
	CFAP77	NM_001282957.2	MANE Select	c.373C>A	p.Arg125Ser	missense	Exon 3 of 6	NP_001269886.1	Q6ZQR2-2
	CFAP77	NM_207417.3		c.481C>A	p.Arg161Ser	missense	Exon 4 of 7	NP_997300.1	Q6ZQR2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP77	ENST00000393216.3	TSL:1 MANE Select	c.373C>A	p.Arg125Ser	missense	Exon 3 of 6	ENSP00000376909.2	Q6ZQR2-2
	CFAP77	ENST00000343036.6	TSL:2	c.481C>A	p.Arg161Ser	missense	Exon 4 of 7	ENSP00000343290.2	Q6ZQR2-1
	CFAP77	ENST00000939325.1		c.373C>A	p.Arg125Ser	missense	Exon 3 of 5	ENSP00000609384.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251364 AF XY: 0.00000736

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.00053
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.88	T
PhyloP100		0.54
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.027	D
Polyphen		0.99	D
Vest4		0.69
MutPred		0.51		Loss of MoRF binding (P = 0.0071)
MVP		0.32
MPC		0.45
ClinPred		0.96	D
GERP RS		1.1
Varity_R		0.21
gMVP		0.84
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs769398138; hg19: chr9-135374836;