9-132410288-G-C

Position:

• chr9-132410288-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001282957.2(CFAP77):​c.17G>C​(p.Ser6Thr) 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: 32)
• Consequence: CFAP77 NM_001282957.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.710

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058792144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP77	NM_001282957.2	c.17G>C	p.Ser6Thr	missense_variant	1/6	ENST00000393216.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP77	ENST00000393216.3	c.17G>C	p.Ser6Thr	missense_variant	1/6	1	NM_001282957.2	P1
CFAP77	ENST00000343036.6	c.17G>C	p.Ser6Thr	missense_variant	1/7	2
CFAP77	ENST00000393215.7	c.17G>C	p.Ser6Thr	missense_variant	1/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jun 29, 2022

The c.17G>C (p.S6T) alteration is located in exon 1 (coding exon 1) of the CFAP77 gene. This alteration results from a G to C substitution at nucleotide position 17, causing the serine (S) at amino acid position 6 to be replaced by a threonine (T). 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	0.076
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.5
DANN	Benign	0.71
DEOGEN2	Benign	0.0019	.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.40	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-0.34	N;N;N
REVEL	Benign	0.0080
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.16
MutPred		0.12		Loss of glycosylation at S6 (P = 0.1401);Loss of glycosylation at S6 (P = 0.1401);Loss of glycosylation at S6 (P = 0.1401);
MVP		0.030
MPC		0.11
ClinPred		0.090	T
GERP RS		-3.8
Varity_R		0.065
gMVP		0.18

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: rs1479188235; hg19: chr9-135285675;