NM_001378189.1:c.1329C>A

Variant names:

• chr1-43198547-C-A
• rs603123
• NM_001378189.1:c.1329C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378189.1(CFAP57):​c.1329C>A​(p.His443Gln) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP57 NM_001378189.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 19 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23040387).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP57	NM_001378189.1	MANE Select	c.1329C>A	p.His443Gln	missense	Exon 8 of 23	NP_001365118.1
	CFAP57	NM_001195831.3		c.1329C>A	p.His443Gln	missense	Exon 8 of 24	NP_001182760.2
	CFAP57	NM_001167965.1		c.1329C>A	p.His443Gln	missense	Exon 8 of 11	NP_001161437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP57	ENST00000372492.9	TSL:5 MANE Select	c.1329C>A	p.His443Gln	missense	Exon 8 of 23	ENSP00000361570.4
	CFAP57	ENST00000533339.1	TSL:1	n.*1228C>A		non_coding_transcript_exon	Exon 9 of 13	ENSP00000432547.1
	CFAP57	ENST00000533339.1	TSL:1	n.*1228C>A		3_prime_UTR	Exon 9 of 13	ENSP00000432547.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 18380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.067
Eigen_PC	Benign	-0.016
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.086
Sift	Benign	0.037	D
Sift4G	Uncertain	0.025	D
Polyphen		0.0070	B
Vest4		0.45
MutPred		0.58		Loss of sheet (P = 0.1158)
MVP		0.10
MPC		0.58
ClinPred		0.82	D
GERP RS		2.9
Varity_R		0.15
gMVP		0.54
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs603123; hg19: chr1-43664218;