chr10-132810455-T-G

Position:

• chr10-132810455-T-G

Variant summary

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

The NM_001200049.3(CFAP46):​c.7618A>C​(p.Ser2540Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2540G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CFAP46 NM_001200049.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.43

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 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=0.05981213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP46	NM_001200049.3	c.7618A>C	p.Ser2540Arg	missense_variant	57/58	ENST00000368586.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP46	ENST00000368586.10	c.7618A>C	p.Ser2540Arg	missense_variant	57/58	5	NM_001200049.3	A2
CFAP46	ENST00000639072.2	c.7755A>C	p.Thr2585=	synonymous_variant	58/59	5		P3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.0020
DANN	Benign	0.78
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0078	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.063
Sift	Uncertain	0.017	D
Sift4G	Benign	0.13	T
Vest4		0.21
MVP		0.014
MPC		0.12
ClinPred		0.10	T
GERP RS		-6.0
Varity_R		0.11
gMVP		0.091

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: rs2254419; hg19: chr10-134623959;