Genetic Variant CFAP410:p.Arg247Leu (chr21-44330229-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_004928.3(CFAP410):c.740G>T(p.Arg247Leu) 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. 13/20 in silico tools predict 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. R247C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

CFAP410
NM_004928.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.152

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

axial spondylometaphyseal dysplasia
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
amyotrophic lateral sclerosis
Inheritance: AD, SD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CFAP410 links:

ENSG00000241728 (HGNC:):

ENSG00000241728 links:

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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=0.07413161).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004928.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP410	NM_004928.3	MANE Select	c.740G>T	p.Arg247Leu	missense	Exon 7 of 7	NP_004919.1	O43822-1
CFAP410	NM_001271441.2		c.1097G>T	p.Arg366Leu	missense	Exon 7 of 7	NP_001258370.1	O43822-4
CFAP410	NM_001271440.2		c.737G>T	p.Arg246Leu	missense	Exon 7 of 7	NP_001258369.1	O43822-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP410	ENST00000339818.9	TSL:1 MANE Select	c.740G>T	p.Arg247Leu	missense	Exon 7 of 7	ENSP00000344566.4	O43822-1
CFAP410	ENST00000397956.7	TSL:1	c.1097G>T	p.Arg366Leu	missense	Exon 7 of 7	ENSP00000381047.3	O43822-4
CFAP410	ENST00000325223.7	TSL:1	c.737G>T	p.Arg246Leu	missense	Exon 7 of 7	ENSP00000317302.7	O43822-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.018

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.026

MetaRNN

Benign

0.074

MetaSVM

Benign

-1.0

PhyloP100

0.15

PROVEAN

Benign

-1.9

REVEL

Benign

0.025

Sift

Benign

0.094

Sift4G

Benign

0.12

Polyphen

0.25

Vest4

0.21

MutPred

0.28

Loss of disorder (P = 0.038)

MVP

0.24

MPC

0.32

ClinPred

0.30

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.054

gMVP

0.058

Mutation Taster

=94/6

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