chr21-44330206-C-T

Position:

chr21-44330206-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004928.3(CFAP410):c.763G>A(p.Ala255Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,568,058 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A255A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 3 hom. )

Consequence

CFAP410
NM_004928.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -1.20

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005149126).

BP6

Variant 21-44330206-C-T is Benign according to our data. Variant chr21-44330206-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 546908.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chr21-44330206-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000663 (101/152368) while in subpopulation NFE AF= 0.00113 (77/68040). AF 95% confidence interval is 0.000928. There are 0 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP410	NM_004928.3 linkuse as main transcript	c.763G>A	p.Ala255Thr	missense_variant	7/7	ENST00000339818.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP410	ENST00000339818.9 linkuse as main transcript	c.763G>A	p.Ala255Thr	missense_variant	7/7	1	NM_004928.3	P4	O43822-1
	ENST00000444409.1 linkuse as main transcript	n.16G>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.000663

AC:

101

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000641

AC:

113

AN:

176270

Hom.:

AF XY:

0.000603

AC XY:

AN XY:

96124

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.000142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000873

Gnomad NFE exome

AF:

0.00128

Gnomad OTH exome

AF:

0.000419

GnomAD4 exome

AF:

0.00143

AC:

2030

AN:

1415690

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

975

AN XY:

701162

show subpopulations

Gnomad4 AFR exome

AF:

0.000275

Gnomad4 AMR exome

AF:

0.000255

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00178

Gnomad4 OTH exome

AF:

0.00107

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152368

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.000786

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000921

AC:

ESP6500EA

AF:

0.00164

AC:

ExAC

AF:

0.000454

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

CFAP410-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 05, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.090

DANN

Benign

0.97

DEOGEN2

Benign

0.0059

T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.54

T;T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.0051

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-0.19

N;N;N

REVEL

Benign

0.0070

Sift

Benign

0.76

T;T;T

Sift4G

Benign

0.36

T;T;T

Polyphen

0.0020

B;.;.

Vest4

0.056

MVP

0.14

MPC

0.32

ClinPred

0.018

GERP RS

-6.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.025

gMVP

0.057

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