1-43181681-A-G

Variant names:

• chr1-43181681-A-G
• NM_001378189.1:c.305A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001378189.1(CFAP57):​c.305A>G​(p.Asn102Ser) 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. 14/20 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: 0.243

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034763098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP57	NM_001378189.1	c.305A>G	p.Asn102Ser	missense_variant	Exon 3 of 23	ENST00000372492.9	NP_001365118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP57	ENST00000372492.9	c.305A>G	p.Asn102Ser	missense_variant	Exon 3 of 23	5	NM_001378189.1	ENSP00000361570.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 21, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.305A>G (p.N102S) alteration is located in exon 3 (coding exon 2) of the CFAP57 gene. This alteration results from a A to G substitution at nucleotide position 305, causing the asparagine (N) at amino acid position 102 to be replaced by a serine (S). 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	0.055
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.2
DANN	Benign	0.51
DEOGEN2	Benign	0.0036	T;.;T;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.035	T;T;T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.45	N;N;.;N
REVEL	Benign	0.021
Sift	Benign	0.67	T;T;.;T
Sift4G	Benign	0.75	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.13
MutPred		0.41		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.040
MPC		0.12
ClinPred		0.050	T
GERP RS		0.24
Varity_R		0.039
gMVP		0.097

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-43647352;