4-2437014-C-A

Variant names:

• chr4-2437014-C-A
• rs112847652
• NM_001193282.4:c.252C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001193282.4(CFAP99):​c.252C>A​(p.Phe84Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,383,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CFAP99 NM_001193282.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 0 publications found

Genes affected

CFAP99 (HGNC:51180): (cilia and flagella associated protein 99) Predicted to be located in motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23060778).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193282.4. 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
	CFAP99	NM_001193282.4	MANE Select	c.252C>A	p.Phe84Leu	missense	Exon 3 of 16	NP_001180211.2	D6REC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP99	ENST00000635017.2	TSL:5 MANE Select	c.252C>A	p.Phe84Leu	missense	Exon 3 of 16	ENSP00000488922.2	D6REC4
	CFAP99	ENST00000511731.5	TSL:1	n.207C>A		non_coding_transcript_exon	Exon 2 of 6
	CFAP99	ENST00000860043.1		c.252C>A	p.Phe84Leu	missense	Exon 3 of 16	ENSP00000530102.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1383690 Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1 AN XY: 682806

African (AFR) AF: 0.00 AC: 0 AN: 31588

American (AMR) AF: 0.00 AC: 0 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35728

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078802

Other (OTH) AF: 0.00 AC: 0 AN: 57896

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.0048	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	4.6
DANN	Benign	0.63
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.23	T
PhyloP100		-2.1
Sift4G	Uncertain	0.040	D
Vest4		0.41
MVP		0.081
GERP RS		-1.8
gMVP		0.44
Mutation Taster		=100/0	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: rs112847652; hg19: chr4-2438741;