dbSNP rs943525127: CFAP99:p.Gln14His (chr4-2426517-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001193282.4(CFAP99):c.42A>C(p.Gln14His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000361 in 1,383,750 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: not found (cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

CFAP99
NM_001193282.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.02

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0836502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP99	NM_001193282.4 link	c.42A>C	p.Gln14His	missense_variant	Exon 2 of 16		NP_001180211.2
CFAP99	XM_047415685.1 link	c.42A>C	p.Gln14His	missense_variant	Exon 2 of 15		XP_047271641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
CFAP99	ENST00000635017.1 link	c.42A>C	p.Gln14His	missense_variant	Exon 2 of 15	5	ENSP00000488922.2	D6REC4
CFAP99	ENST00000382849.2 link	n.179A>C		non_coding_transcript_exon_variant	Exon 2 of 3	2
CFAP99	ENST00000511731.5 link	n.-4A>C		upstream_gene_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000743

AC:

AN:

134598

Hom.:

AF XY:

0.00

AC XY:

AN XY:

73302

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:

0.0000189

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000361

AC:

AN:

1383750

Hom.:

Cov.:

AF XY:

0.00000439

AC XY:

AN XY:

682822

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000463

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.42A>C (p.Q14H) alteration is located in exon 2 (coding exon 1) of the CFAP99 gene. This alteration results from a A to C substitution at nucleotide position 42, causing the glutamine (Q) at amino acid position 14 to be replaced by a histidine (H). 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

-0.18

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.43

DANN

Benign

0.55

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.42

T;T

MetaRNN

Benign

0.084

T;T

Sift4G

Benign

0.14

T;T

Vest4

0.17

MVP

0.061

GERP RS

-6.2

gMVP

0.29

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