9-132410452-C-A

Variant names:

• chr9-132410452-C-A
• rs930230672
• NM_001282957.2:c.181C>A

Variant summary

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

The NM_001282957.2(CFAP77):​c.181C>A​(p.Pro61Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000189 in 1,585,502 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. P61A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CFAP77 NM_001282957.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.19
• 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]

LOC105376304 (HGNC:):

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.181C>A	p.Pro61Thr	missense	Exon 1 of 6	NP_001269886.1	Q6ZQR2-2
	CFAP77	NM_207417.3		c.181C>A	p.Pro61Thr	missense	Exon 1 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.181C>A	p.Pro61Thr	missense	Exon 1 of 6	ENSP00000376909.2	Q6ZQR2-2
	CFAP77	ENST00000343036.6	TSL:2	c.181C>A	p.Pro61Thr	missense	Exon 1 of 7	ENSP00000343290.2	Q6ZQR2-1
	CFAP77	ENST00000939325.1		c.181C>A	p.Pro61Thr	missense	Exon 1 of 5	ENSP00000609384.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152100 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1433402 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 712852

African (AFR) AF: 0.00 AC: 0 AN: 29694

American (AMR) AF: 0.00 AC: 0 AN: 42372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25028

East Asian (EAS) AF: 0.00 AC: 0 AN: 35618

South Asian (SAS) AF: 0.00 AC: 0 AN: 83494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1100598

Other (OTH) AF: 0.00 AC: 0 AN: 59102

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152100 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74290

African (AFR) AF: 0.0000241 AC: 1 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.46	T
PhyloP100		4.2
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.17
Sift	Benign	0.053	T
Sift4G	Benign	0.27	T
Polyphen		0.88	P
Vest4		0.62
MutPred		0.54		Gain of sheet (P = 0.0477)
MVP		0.68
MPC		0.16
ClinPred		0.98	D
GERP RS		4.7
PromoterAI		-0.00040	Neutral
Varity_R		0.38
gMVP		0.42
Mutation Taster		=74/26	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: rs930230672; hg19: chr9-135285839;