NM_001378189.1:c.434C>T

Variant names:

• chr1-43181810-C-T
• NM_001378189.1:c.434C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001378189.1(CFAP57):​c.434C>T​(p.Ala145Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A145T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP57 NM_001378189.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.12
• Publications: 0 publications found

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]

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]

LOC105378685 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP57	NM_001378189.1	MANE Select	c.434C>T	p.Ala145Val	missense	Exon 3 of 23	NP_001365118.1	Q96MR6-1
	CFAP57	NM_001195831.3		c.434C>T	p.Ala145Val	missense	Exon 3 of 24	NP_001182760.2	A0A087WVY5
	CFAP57	NM_001167965.1		c.434C>T	p.Ala145Val	missense	Exon 3 of 11	NP_001161437.1	Q96MR6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP57	ENST00000372492.9	TSL:5 MANE Select	c.434C>T	p.Ala145Val	missense	Exon 3 of 23	ENSP00000361570.4	Q96MR6-1
	CFAP57	ENST00000533339.1	TSL:1	n.*333C>T		non_coding_transcript_exon	Exon 4 of 13	ENSP00000432547.1	E9PP89
	CFAP57	ENST00000533339.1	TSL:1	n.*333C>T		3_prime_UTR	Exon 4 of 13	ENSP00000432547.1	E9PP89

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	CFAP57-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.10	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.32	T
PhyloP100		7.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.018	D
Polyphen		0.90	P
Vest4		0.73
MutPred		0.48		Loss of sheet (P = 0.0817)
MVP		0.31
MPC		0.64
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.45
gMVP		0.55
Mutation Taster		=43/57	disease causing

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

Other links and lift over

hg19: chr1-43647481;