Genetic Variant CFAP57:p.Val169Met (chr1-43183621-G-A) – ACMG Classification: Uncertain_significance (0 pts)

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>A(p.Val169Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Consequence

CFAP57
NM_001378189.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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=0.18543682).

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>A	p.Val169Met	missense	Exon 4 of 23	NP_001365118.1	Q96MR6-1
CFAP57	NM_001195831.3		c.505G>A	p.Val169Met	missense	Exon 4 of 24	NP_001182760.2	A0A087WVY5
CFAP57	NM_001167965.1		c.505G>A	p.Val169Met	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>A	p.Val169Met	missense	Exon 4 of 23	ENSP00000361570.4	Q96MR6-1
CFAP57	ENST00000533339.1	TSL:1	n.*404G>A		non_coding_transcript_exon	Exon 5 of 13	ENSP00000432547.1	E9PP89
CFAP57	ENST00000533339.1	TSL:1	n.*404G>A		3_prime_UTR	Exon 5 of 13	ENSP00000432547.1	E9PP89

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.010

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

PhyloP100

0.28

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.2

REVEL

Benign

0.042

Sift

Benign

0.18

Sift4G

Benign

0.13

Polyphen

0.078

Vest4

0.15

MutPred

0.47

Gain of disorder (P = 0.1358)

MVP

0.076

MPC

0.22

ClinPred

0.15

GERP RS

-2.1

Varity_R

0.047

gMVP

0.32

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over