Variant 12-121923814-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_144668.6(CFAP251):c.571C>G(p.Gln191Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CFAP251
NM_144668.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.507

Variant links:

Genes affected

CFAP251 (HGNC:28506): (cilia and flagella associated protein 251) This protein encoded by this gene belongs to the WD repeat-containing family of proteins, which function in the formation of protein-protein complexes in a variety of biological pathways. This family member appears to function in the determination of mean platelet volume (MPV), and polymorphisms in this gene have been associated with variance in MPV. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2011]

CFAP251 links:

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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=0.07403764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP251	NM_144668.6 linkuse as main transcript	c.571C>G	p.Gln191Glu	missense_variant	3/22	ENST00000288912.9	NP_653269.3
CFAP251	NM_001178003.2 linkuse as main transcript	c.571C>G	p.Gln191Glu	missense_variant	3/18		NP_001171474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP251	ENST00000288912.9 linkuse as main transcript	c.571C>G	p.Gln191Glu	missense_variant	3/22	1	NM_144668.6	ENSP00000288912		Q8TBY9-1
CFAP251	ENST00000397454.2 linkuse as main transcript	c.571C>G	p.Gln191Glu	missense_variant	3/18	1		ENSP00000380595	P1	Q8TBY9-2
CFAP251	ENST00000540779.1 linkuse as main transcript	n.469C>G		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249556

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 27, 2023

The c.571C>G (p.Q191E) alteration is located in exon 3 (coding exon 2) of the WDR66 gene. This alteration results from a C to G substitution at nucleotide position 571, causing the glutamine (Q) at amino acid position 191 to be replaced by a glutamic acid (E). 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

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.058

DANN

Benign

0.57

DEOGEN2

Benign

0.0050

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.074

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.023

Sift

Benign

0.077

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.26

B;.

Vest4

0.069

MutPred

0.33

Gain of catalytic residue at M189 (P = 0.0015);Gain of catalytic residue at M189 (P = 0.0015);

MVP

0.10

MPC

0.14

ClinPred

0.081

GERP RS

0.11

Varity_R

0.062

gMVP

0.083

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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