1-43183621-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001378189.1(CFAP57):c.505G>C(p.Val169Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V169M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CFAP57
NM_001378189.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.281

Publications

0 publications found

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:15531): (EBNA1 binding protein 2) Enables RNA binding activity. Predicted to be involved in rRNA processing and ribosomal large subunit biogenesis. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

EBNA1BP2 links:

LOC105378685 (HGNC:):

LOC105378685 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.109638244).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378189.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP57	NM_001378189.1	MANE Select	c.505G>C	p.Val169Leu	missense	Exon 4 of 23	NP_001365118.1	Q96MR6-1
CFAP57	NM_001195831.3		c.505G>C	p.Val169Leu	missense	Exon 4 of 24	NP_001182760.2	A0A087WVY5
CFAP57	NM_001167965.1		c.505G>C	p.Val169Leu	missense	Exon 4 of 11	NP_001161437.1	Q96MR6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP57	ENST00000372492.9	TSL:5 MANE Select	c.505G>C	p.Val169Leu	missense	Exon 4 of 23	ENSP00000361570.4	Q96MR6-1
CFAP57	ENST00000533339.1	TSL:1	n.*404G>C		non_coding_transcript_exon	Exon 5 of 13	ENSP00000432547.1	E9PP89
CFAP57	ENST00000533339.1	TSL:1	n.*404G>C		3_prime_UTR	Exon 5 of 13	ENSP00000432547.1	E9PP89

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000795

AC:

AN:

251418

AF XY:

0.00000736

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111992

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.0

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.013

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.70

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0065

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.93

PhyloP100

0.28

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.73

REVEL

Benign

0.033

Sift

Benign

0.63

Sift4G

Benign

0.53

Polyphen

0.0

Vest4

0.079

MutPred

0.41

Gain of sheet (P = 0.1945)

MVP

0.040

MPC

0.15

ClinPred

0.028

GERP RS

-2.1

Varity_R

0.055

gMVP

0.28

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over