chr21-44330245-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004928.3(CFAP410):c.724C>T(p.Arg242Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,443,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R242Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

CFAP410
NM_004928.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

Variant links:

Genes affected

CFAP410 (HGNC:1260): (cilia and flagella associated protein 410) Four alternatively spliced transcript variants encoding four different isoforms have been found for this nuclear gene. All isoforms contain leucine-rich repeats. Three of these isoforms are mitochondrial proteins and one of them lacks the target peptide, so is not located in mitochondrion. This gene is down-regulated in Down syndrome (DS) brain, which may represent mitochondrial dysfunction in DS patients. [provided by RefSeq, Sep 2012]

CFAP410 links:

ENSG00000241728 (HGNC:):

ENSG00000241728 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2540892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP410	NM_004928.3 link	c.724C>T	p.Arg242Trp	missense_variant	Exon 7 of 7	ENST00000339818.9	NP_004919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP410	ENST00000339818.9 link	c.724C>T	p.Arg242Trp	missense_variant	Exon 7 of 7	1	NM_004928.3	ENSP00000344566.4		O43822-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000142

AC:

AN:

211136

AF XY:

0.0000173

show subpopulations

Gnomad AFR exome

AF:

0.0000778

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000613

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000109

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000139

AC:

AN:

1443156

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

716616

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

33262

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

42674

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25776

Gnomad4 EAS exome

AF:

0.0000512

AC:

AN:

39046

Gnomad4 SAS exome

AF:

0.0000119

AC:

AN:

83842

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

48058

Gnomad4 NFE exome

AF:

0.0000154

AC:

AN:

1105110

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

59730

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000332

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jul 26, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1500883). This variant has not been reported in the literature in individuals affected with CFAP410-related conditions. This variant is present in population databases (rs780412319, gnomAD 0.008%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 242 of the CFAP410 protein (p.Arg242Trp). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

T;.;.

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Uncertain

-0.23

PROVEAN

Uncertain

-4.1

D;D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.28

MutPred

0.43

Loss of disorder (P = 0);.;.;

MVP

0.72

MPC

0.35

ClinPred

0.88

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.54

Mutation Taster

=74/26

polymorphism

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over