Variant chr4-2445301-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001193282.4(CFAP99):c.635C>G(p.Pro212Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000305 in 1,349,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

CFAP99
NM_001193282.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

Variant links:

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]

CFAP99 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.023274839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP99	NM_001193282.4 linkuse as main transcript	c.635C>G	p.Pro212Arg	missense_variant	6/16	ENST00000635017.2
CFAP99	XM_047415685.1 linkuse as main transcript	c.635C>G	p.Pro212Arg	missense_variant	6/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CFAP99	ENST00000635017.2 linkuse as main transcript	c.635C>G	p.Pro212Arg	missense_variant	6/16	5	NM_001193282.4	P1
CFAP99	ENST00000511731.5 linkuse as main transcript	n.419+2059C>G		intron_variant, non_coding_transcript_variant		1
CFAP99	ENST00000514556.5 linkuse as main transcript	n.217C>G		non_coding_transcript_exon_variant	2/4	5
CFAP99	ENST00000515732.1 linkuse as main transcript	n.199C>G		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000379

AC:

AN:

21086

Hom.:

AF XY:

0.000470

AC XY:

AN XY:

10632

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000684

Gnomad OTH exome

AF:

0.00145

GnomAD4 exome

AF:

0.000316

AC:

378

AN:

1197032

Hom.:

Cov.:

AF XY:

0.000318

AC XY:

184

AN XY:

579126

show subpopulations

Gnomad4 AFR exome

AF:

0.0000405

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000108

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000344

Gnomad4 OTH exome

AF:

0.000344

GnomAD4 genome

AF:

0.000223

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000129

Hom.:

Bravo

AF:

0.000253

ExAC

AF:

0.000180

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2022

The c.635C>G (p.P212R) alteration is located in exon 6 (coding exon 5) of the CFAP99 gene. This alteration results from a C to G substitution at nucleotide position 635, causing the proline (P) at amino acid position 212 to be replaced by an arginine (R). 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

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.66

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.60

T;T

MetaRNN

Benign

0.023

T;T

Sift4G

Benign

0.063

T;T

Vest4

0.10

MVP

0.39

GERP RS

3.6

gMVP

0.21

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over