Variant 12-121921387-C-T 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_144668.6(CFAP251):c.82C>T(p.Pro28Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,611,476 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: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CFAP251
NM_144668.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.32

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:

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=0.050738454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP251	NM_144668.6 linkuse as main transcript	c.82C>T	p.Pro28Ser	missense_variant	2/22	ENST00000288912.9	NP_653269.3
CFAP251	NM_001178003.2 linkuse as main transcript	c.82C>T	p.Pro28Ser	missense_variant	2/18		NP_001171474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP251	ENST00000288912.9 linkuse as main transcript	c.82C>T	p.Pro28Ser	missense_variant	2/22	1	NM_144668.6	ENSP00000288912		Q8TBY9-1
CFAP251	ENST00000397454.2 linkuse as main transcript	c.82C>T	p.Pro28Ser	missense_variant	2/18	1		ENSP00000380595	P1	Q8TBY9-2
CFAP251	ENST00000540779.1 linkuse as main transcript			upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000734

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248336

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134940

show subpopulations

Gnomad AFR exome

AF:

0.0000652

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460658

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726620

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150818

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73566

show subpopulations

Gnomad4 AFR

AF:

0.0000734

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.00000827

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

Oct 05, 2023

The c.82C>T (p.P28S) alteration is located in exon 2 (coding exon 1) of the WDR66 gene. This alteration results from a C to T substitution at nucleotide position 82, causing the proline (P) at amino acid position 28 to be replaced by a serine (S). 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

0.080

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.6

DANN

Benign

0.66

DEOGEN2

Benign

0.0058

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.43

T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.13

Sift

Benign

0.052

T;D

Sift4G

Benign

0.42

T;T

Polyphen

0.0

B;.

Vest4

0.084

MutPred

0.17

Gain of phosphorylation at P28 (P = 0.0113);Gain of phosphorylation at P28 (P = 0.0113);

MVP

0.048

MPC

0.13

ClinPred

0.084

GERP RS

-4.6

Varity_R

0.041

gMVP

0.10

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