NM_001200049.3:c.7897G>T

Variant names:

• chr10-132808672-C-A
• rs116078472
• NM_001200049.3:c.7897G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001200049.3(CFAP46):​c.7897G>T​(p.Ala2633Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,429,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A2633T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CFAP46 NM_001200049.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.11
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05722946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP46	NM_001200049.3	c.7897G>T	p.Ala2633Ser	missense_variant	Exon 58 of 58	ENST00000368586.10	NP_001186978.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP46	ENST00000368586.10	c.7897G>T	p.Ala2633Ser	missense_variant	Exon 58 of 58	5	NM_001200049.3	ENSP00000357575.4
CFAP46	ENST00000639072.2	c.*120G>T		3_prime_UTR_variant	Exon 59 of 59	5		ENSP00000491877.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000103 AC: 2 AN: 193608 AF XY: 0.0000190

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000556

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1429482 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 708552

African (AFR) AF: 0.00 AC: 0 AN: 32626

American (AMR) AF: 0.00 AC: 0 AN: 38906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25636

East Asian (EAS) AF: 0.00 AC: 0 AN: 37794

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5540

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095580

Other (OTH) AF: 0.00 AC: 0 AN: 59264

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0020
DANN	Benign	0.31
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0045	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
PhyloP100		-4.1
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.0070
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.30	T
Vest4		0.024
MVP		0.014
MPC		0.098
ClinPred		0.047	T
GERP RS		-2.6
Varity_R		0.073
gMVP		0.021
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs116078472; hg19: chr10-134622176;