10-104131391-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025145.7(CFAP43):c.4771T>G(p.Cys1591Gly) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C1591R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP43 NM_025145.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.02

Genes affected

CFAP43 (HGNC:26684): (cilia and flagella associated protein 43) This gene encodes a member of the cilia- and flagella-associated protein family. [provided by RefSeq, Sep 2016]

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=0.22743136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP43	NM_025145.7	c.4771T>G	p.Cys1591Gly	missense_variant	37/38	ENST00000357060.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP43	ENST00000357060.8	c.4771T>G	p.Cys1591Gly	missense_variant	37/38	1	NM_025145.7	P1
CFAP43	ENST00000434629.5	c.2767T>G	p.Cys923Gly	missense_variant	22/23	1
CFAP43	ENST00000457071.5	c.1318T>G	p.Cys440Gly	missense_variant	11/12	2

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2024

The c.4771T>G (p.C1591G) alteration is located in exon 37 (coding exon 37) of the CFAP43 gene. This alteration results from a T to G substitution at nucleotide position 4771, causing the cysteine (C) at amino acid position 1591 to be replaced by a glycine (G). 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	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	21
Dann	Benign	0.93
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.092
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.89	N;N
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.15
Sift	Benign	0.31	T
Sift4G	Benign	0.17	T
Polyphen		0.058	B
Vest4		0.45
MutPred		0.62		Gain of relative solvent accessibility (P = 0.0023);
MVP		0.29
MPC		0.17
ClinPred		0.64	D
GERP RS		5.7
Varity_R		0.27
gMVP		0.090

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: chr10-105891149;