9-132482338-C-T

Variant names:

• chr9-132482338-C-T
• NM_001282957.2:c.196-16357C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207417.3(CFAP77):​c.224C>T​(p.Ser75Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: CFAP77 NM_207417.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.137

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.080331415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP77	NM_001282957.2	c.196-16357C>T		intron_variant	Intron 1 of 5	ENST00000393216.3	NP_001269886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP77	ENST00000393216.3	c.196-16357C>T		intron_variant	Intron 1 of 5	1	NM_001282957.2	ENSP00000376909.2
CFAP77	ENST00000343036.6	c.224C>T	p.Ser75Phe	missense_variant	Exon 2 of 7	2		ENSP00000343290.2
CFAP77	ENST00000393215.7	c.196-16357C>T		intron_variant	Intron 1 of 3	5		ENSP00000376908.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.224C>T (p.S75F) alteration is located in exon 2 (coding exon 2) of the CFAP77 gene. This alteration results from a C to T substitution at nucleotide position 224, causing the serine (S) at amino acid position 75 to be replaced by a phenylalanine (F). 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	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.8
DANN	Benign	0.80
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.99	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.0090
Sift	Benign	0.068	T
Sift4G	Benign	0.086	T
Polyphen		0.021	B
Vest4		0.21
MutPred		0.39		Loss of disorder (P = 0.0019);
MVP		0.040
MPC		0.14
ClinPred		0.072	T
GERP RS		-0.29
Varity_R		0.039
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-135357725;