1-43183621-G-A

Position:

• chr1-43183621-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/20 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.281

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]

LOC105378685 (HGNC:):

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18543682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP57	NM_001378189.1	c.505G>A	p.Val169Met	missense_variant	4/23	ENST00000372492.9	NP_001365118.1
LOC105378685	XR_007066041.1	n.670-1837C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP57	ENST00000372492.9	c.505G>A	p.Val169Met	missense_variant	4/23	5	NM_001378189.1	ENSP00000361570	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

The c.505G>A (p.V169M) alteration is located in exon 4 (coding exon 3) of the CFAP57 gene. This alteration results from a G to A substitution at nucleotide position 505, causing the valine (V) at amino acid position 169 to be replaced by a methionine (M). 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	Benign	0.20
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T;.;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.62	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.2	N;N;.
REVEL	Benign	0.042
Sift	Benign	0.18	T;D;.
Sift4G	Benign	0.13	T;D;T
Polyphen		0.078	B;B;.
Vest4		0.15
MutPred		0.47		Gain of disorder (P = 0.1358);Gain of disorder (P = 0.1358);Gain of disorder (P = 0.1358);
MVP		0.076
MPC		0.22
ClinPred		0.15	T
GERP RS		-2.1
Varity_R		0.047
gMVP		0.32

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

LitVar

Other links and lift over

dbSNP: rs767278420; hg19: chr1-43649292;