10-132810455-T-C

Position:

• chr10-132810455-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001200049.3(CFAP46):​c.7618A>G​(p.Ser2540Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,613,188 control chromosomes in the GnomAD database, including 397,900 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.75 (44546 hom., cov: 33)
  • Exomes 𝑓: 0.69 (353354 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0957259E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP46	NM_001200049.3	c.7618A>G	p.Ser2540Gly	missense_variant	57/58	ENST00000368586.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP46	ENST00000368586.10	c.7618A>G	p.Ser2540Gly	missense_variant	57/58	5	NM_001200049.3	A2
CFAP46	ENST00000639072.2	c.7755A>G	p.Thr2585=	synonymous_variant	58/59	5		P3

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114602 AN: 152044 Hom.: 44484 Cov.: 33

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.720

GnomAD3 exomes AF: 0.680 AC: 168973 AN: 248426 Hom.: 59611 AF XY: 0.687 AC XY: 92510 AN XY: 134658

Gnomad AFR exome AF: 0.943

Gnomad AMR exome AF: 0.412

Gnomad ASJ exome AF: 0.756

Gnomad EAS exome AF: 0.734

Gnomad SAS exome AF: 0.705

Gnomad FIN exome AF: 0.737

Gnomad NFE exome AF: 0.692

Gnomad OTH exome AF: 0.676

GnomAD4 exome AF: 0.692 AC: 1011024 AN: 1461026 Hom.: 353354 Cov.: 57 AF XY: 0.693 AC XY: 503838 AN XY: 726850

Gnomad4 AFR exome AF: 0.946

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.756

Gnomad4 EAS exome AF: 0.733

Gnomad4 SAS exome AF: 0.705

Gnomad4 FIN exome AF: 0.736

Gnomad4 NFE exome AF: 0.688

Gnomad4 OTH exome AF: 0.710

GnomAD4 genome AF: 0.754 AC: 114712 AN: 152162 Hom.: 44546 Cov.: 33 AF XY: 0.749 AC XY: 55701 AN XY: 74372

Gnomad4 AFR AF: 0.939

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.723

Alfa AF: 0.704 Hom.: 67232

Bravo AF: 0.749

TwinsUK AF: 0.694 AC: 2575

ALSPAC AF: 0.674 AC: 2596

ESP6500AA AF: 0.937 AC: 4128

ESP6500EA AF: 0.690 AC: 5933

ExAC AF: 0.694 AC: 84292

Asia WGS AF: 0.728 AC: 2530 AN: 3478

EpiCase AF: 0.693

EpiControl AF: 0.692

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0010
DANN	Benign	0.22
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.011
Sift	Benign	0.058	T
Sift4G	Benign	0.39	T
Vest4		0.036
MPC		0.098
ClinPred		0.0055	T
GERP RS		-6.0
Varity_R		0.036
gMVP		0.042

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: rs2254419; hg19: chr10-134623959; COSMIC: COSV54155884;