4-185175815-C-T

Variant names:

• chr4-185175815-C-T
• rs199734613
• NM_020827.3:c.1291G>A

Variant summary

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

The NM_020827.3(CFAP97):​c.1291G>A​(p.Glu431Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. E431Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP97 NM_020827.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.20
• Publications: 2 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.1291G>A	p.Glu431Lys	missense_variant	Exon 3 of 5	ENST00000458385.7	NP_065878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP97	ENST00000458385.7	c.1291G>A	p.Glu431Lys	missense_variant	Exon 3 of 5	2	NM_020827.3	ENSP00000409964.2
CFAP97	ENST00000514798.1	c.1291G>A	p.Glu431Lys	missense_variant	Exon 3 of 4	1		ENSP00000423312.1
CFAP97	ENST00000502992.1	n.579G>A		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Benign	-0.0011	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.071	T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.75	T
PhyloP100		5.2
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.23
Sift	Benign	0.056	T;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.57
MutPred		0.19		Gain of MoRF binding (P = 0.0141);Gain of MoRF binding (P = 0.0141);
MVP		0.77
MPC		0.12
ClinPred		0.97	D
GERP RS		6.2
Varity_R		0.21
gMVP		0.72
Mutation Taster		=32/68	disease causing

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: rs199734613; hg19: chr4-186096969;