1-43181758-C-T

Position:

• chr1-43181758-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001378189.1(CFAP57):​c.382C>T​(p.Pro128Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000242 in 1,614,162 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: CFAP57 NM_001378189.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013374507).
• BS2: High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP57	NM_001378189.1	c.382C>T	p.Pro128Ser	missense_variant	3/23	ENST00000372492.9	NP_001365118.1
LOC105378685	XR_007066041.1	n.696G>A		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP57	ENST00000372492.9	c.382C>T	p.Pro128Ser	missense_variant	3/23	5	NM_001378189.1	ENSP00000361570	P1

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000274 AC: 69 AN: 251402 Hom.: 0 AF XY: 0.000287 AC XY: 39 AN XY: 135880

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000440

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000249 AC: 364 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.000263 AC XY: 191 AN XY: 727240

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00161

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000543

Gnomad4 NFE exome AF: 0.000249

Gnomad4 OTH exome AF: 0.000215

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15 AN XY: 74460

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000333 Hom.: 0

Bravo AF: 0.000125

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000296 AC: 36

EpiCase AF: 0.000327

EpiControl AF: 0.000296

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

Dec 27, 2022

The c.382C>T (p.P128S) alteration is located in exon 3 (coding exon 2) of the CFAP57 gene. This alteration results from a C to T substitution at nucleotide position 382, causing the proline (P) at amino acid position 128 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	0.070
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.0032	T;.;T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.013	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.80	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.15	N;N;.;N
REVEL	Benign	0.038
Sift	Benign	0.74	T;T;.;T
Sift4G	Benign	0.70	T;T;T;T
Polyphen		0.0020	B;B;.;.
Vest4		0.21
MVP		0.067
MPC		0.15
ClinPred		0.027	T
GERP RS		2.4
Varity_R		0.044
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs143229697; hg19: chr1-43647429;