10-132808453-T-C

Position:

• chr10-132808453-T-C

Variant summary

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

The NM_001200049.3(CFAP46):​c.8116A>G​(p.Thr2706Ala) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP46 NM_001200049.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0540

Genes affected

CFAP46 (HGNC:25247): (cilia and flagella associated protein 46) Predicted to be involved in axoneme assembly. Predicted to be located in axoneme. [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=0.076105416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP46	NM_001200049.3	c.8116A>G	p.Thr2706Ala	missense_variant	58/58	ENST00000368586.10	NP_001186978.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP46	ENST00000368586.10	c.8116A>G	p.Thr2706Ala	missense_variant	58/58	5	NM_001200049.3	ENSP00000357575.4
CFAP46	ENST00000639072.2	c.*339A>G		3_prime_UTR_variant	59/59	5		ENSP00000491877.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

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 06, 2024

The c.3052A>G (p.T1018A) alteration is located in exon 23 (coding exon 23) of the CFAP46 gene. This alteration results from a A to G substitution at nucleotide position 3052, causing the threonine (T) at amino acid position 1018 to be replaced by an alanine (A). 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	0.059
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.30
DANN	Benign	0.88
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0050	N
LIST_S2	Benign	0.18	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.011
Sift	Pathogenic	0.0	D
Vest4		0.023
MVP		0.014
MPC		0.11
ClinPred		0.046	T
GERP RS		-0.95
Varity_R		0.043
gMVP		0.026

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: rs1847502771; hg19: chr10-134621957;