Genetic Variant CFAP184:p.Val268Met (chr4-7042137-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153376.3(CFAP184):c.802G>A(p.Val268Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. V268L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CFAP184
NM_153376.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.290

Publications

0 publications found

Variant links:

Genes affected

CFAP184 (HGNC:26900): (cilia and flagella associated protein 184) Predicted to be involved in cilium assembly. Predicted to be active in axoneme and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

CFAP184 links:

TADA2B (HGNC:30781): (transcriptional adaptor 2B) TADA2B functions as a transcriptional adaptor protein that potentiates transcription through coordination of histone acetyltransferase (HAT) activity and by linking activation factors to basal transcriptional machinery (Barlev et al., 2003 [PubMed 12972612]).[supplied by OMIM, Apr 2010]

TADA2B links:

ENSG00000245748 (HGNC:58725):

ENSG00000245748 links:

LOC100129931 (HGNC:):

LOC100129931 links:

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ACMG classification

Classification was made for transcript

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=0.06499919).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153376.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP184	NM_153376.3	MANE Select	c.802G>A	p.Val268Met	missense	Exon 1 of 1	NP_699207.1	Q2M329
	LOC100129931	NR_033828.1		n.696+2843G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP184	ENST00000310085.6	TSL:6 MANE Select	c.802G>A	p.Val268Met	missense	Exon 1 of 1	ENSP00000309285.4	Q2M329
TADA2B	ENST00000506692.1	TSL:2	c.-7+51C>T		intron	N/A	ENSP00000422398.1	D6RC20
ENSG00000245748	ENST00000500031.1	TSL:2	n.696+2843G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1453808

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723454

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33220

American (AMR)

AF:

0.00

AC:

AN:

43850

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25952

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48280

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110750

Other (OTH)

AF:

0.00

AC:

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.6

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.028

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.47

M_CAP

Benign

0.012

MetaRNN

Benign

0.065

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.90

PhyloP100

-0.29

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.080

REVEL

Benign

0.061

Sift

Benign

0.22

Sift4G

Benign

0.11

Polyphen

0.53

Vest4

0.036

MutPred

0.22

Gain of catalytic residue at V268 (P = 0.0541)

MVP

0.040

ClinPred

0.33

GERP RS

3.3

PromoterAI

0.035

Neutral

(source)

Varity_R

0.038

gMVP

0.27

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over