10-104140889-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_025145.7(CFAP43):c.4384A>G(p.Ile1462Val) 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. 12/20 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: CFAP43 NM_025145.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.43

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27445942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP43	NM_025145.7	c.4384A>G	p.Ile1462Val	missense_variant	34/38	ENST00000357060.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP43	ENST00000357060.8	c.4384A>G	p.Ile1462Val	missense_variant	34/38	1	NM_025145.7	P1
CFAP43	ENST00000434629.5	c.2380A>G	p.Ile794Val	missense_variant	19/23	1
CFAP43	ENST00000457071.5	c.931A>G	p.Ile311Val	missense_variant	8/12	2
CFAP43	ENST00000479392.1	n.148A>G		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Aug 22, 2022

The c.4384A>G (p.I1462V) alteration is located in exon 34 (coding exon 34) of the CFAP43 gene. This alteration results from a A to G substitution at nucleotide position 4384, causing the isoleucine (I) at amino acid position 1462 to be replaced by a valine (V). 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	0.074
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.93	D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.027
Sift	Uncertain	0.018	D
Sift4G	Benign	0.18	T
Polyphen		0.81	P
Vest4		0.090
MutPred		0.28		Loss of helix (P = 0.0626);
MVP		0.24
MPC		0.25
ClinPred		0.52	D
GERP RS		5.4
Varity_R		0.15
gMVP		0.061

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1261762303; hg19: chr10-105900647;