NM_020827.3:c.1409A>T

Variant names:

• chr4-185164091-T-A
• NM_020827.3:c.1409A>T

Variant summary

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

The NM_020827.3(CFAP97):​c.1409A>T​(p.Tyr470Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y470C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CFAP97 NM_020827.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.83
• Publications: 0 publications found

Genes affected

CFAP97 (HGNC:29276): (cilia and flagella associated protein 97)

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
CFAP97	NM_020827.3	c.1409A>T	p.Tyr470Phe	missense_variant	Exon 4 of 5	ENST00000458385.7	NP_065878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP97	ENST00000458385.7	c.1409A>T	p.Tyr470Phe	missense_variant	Exon 4 of 5	2	NM_020827.3	ENSP00000409964.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1409A>T (p.Y470F) alteration is located in exon 4 (coding exon 3) of the CFAP97 gene. This alteration results from a A to T substitution at nucleotide position 1409, causing the tyrosine (Y) at amino acid position 470 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	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.066	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.89	T
PhyloP100		4.8
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.14
Sift	Benign	0.060	T
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.72
MutPred		0.32		Gain of glycosylation at Y470 (P = 0.0278);
MVP		0.76
MPC		0.13
ClinPred		0.81	D
GERP RS		5.5
Varity_R		0.12
gMVP		0.35
Mutation Taster		=94/6	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

hg19: chr4-186085245;