4-2445180-G-C

Variant names:

• chr4-2445180-G-C
• rs773210785
• NM_001193282.4:c.514G>C

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.514G>C​(p.Ala172Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000787 in 1,271,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/10 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A172T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: CFAP99 NM_001193282.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• 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=0.10596028).

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.514G>C	p.Ala172Pro	missense	Exon 6 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.514G>C	p.Ala172Pro	missense	Exon 6 of 16	ENSP00000488922.2	D6REC4
	CFAP99	ENST00000511731.5	TSL:1	n.419+1938G>C		intron	N/A
	CFAP99	ENST00000860043.1		c.514G>C	p.Ala172Pro	missense	Exon 6 of 16	ENSP00000530102.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.87e-7 AC: 1 AN: 1271412 Hom.: 0 Cov.: 30 AF XY: 0.00000161 AC XY: 1 AN XY: 622690

African (AFR) AF: 0.00 AC: 0 AN: 26480

American (AMR) AF: 0.0000524 AC: 1 AN: 19080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19554

East Asian (EAS) AF: 0.00 AC: 0 AN: 30294

South Asian (SAS) AF: 0.00 AC: 0 AN: 60330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5224

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1026972

Other (OTH) AF: 0.00 AC: 0 AN: 53048

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.43
DANN	Benign	0.72
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.11	T
PhyloP100		-0.038
Sift4G	Uncertain	0.049	D
Vest4		0.13
MVP		0.29
GERP RS		-2.1
gMVP		0.33
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs773210785; hg19: chr4-2446907;