Variant chr1-43172903-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001378189.1(CFAP57):c.150C>A(p.Phe50Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CFAP57
NM_001378189.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

Variant links:

Genes affected

CFAP57 (HGNC:26485): (cilia and flagella associated protein 57) 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 is thought to function in craniofacial development, possibly in the fusion of lip and palate. A missense mutation in this gene is associated with Van der Woude syndrome 2. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

CFAP57 links:

EBNA1BP2 (HGNC:):

EBNA1BP2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.28010407).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP57	NM_001378189.1 linkuse as main transcript	c.150C>A	p.Phe50Leu	missense_variant	2/23	ENST00000372492.9	NP_001365118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP57	ENST00000372492.9 linkuse as main transcript	c.150C>A	p.Phe50Leu	missense_variant	2/23	5	NM_001378189.1	ENSP00000361570.4		Q96MR6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727146

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

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

Nov 22, 2024

The c.150C>A (p.F50L) alteration is located in exon 2 (coding exon 1) of the CFAP57 gene. This alteration results from a C to A substitution at nucleotide position 150, causing the phenylalanine (F) at amino acid position 50 to be replaced by a leucine (L). 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

Pathogenic

0.88

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.;T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.012

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.80

T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.28

T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-4.4

D;D;.;D

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;T;.;T

Sift4G

Benign

0.16

T;T;T;T

Polyphen

0.15

.;B;.;.

Vest4

0.39

MutPred

0.34

Gain of ubiquitination at K46 (P = 0.1084);Gain of ubiquitination at K46 (P = 0.1084);Gain of ubiquitination at K46 (P = 0.1084);Gain of ubiquitination at K46 (P = 0.1084);

MVP

0.24

MPC

0.55

ClinPred

1.0

GERP RS

3.4

Varity_R

0.88

gMVP

0.45

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over