Genetic Variant NM_004928.3:c.762C>A (chr21-44330207-G-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_004928.3(CFAP410):c.762C>A(p.His254Gln) 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. 14/20 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. H254R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CFAP410
NM_004928.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.552

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: 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=0.03922388).

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.762C>A	p.His254Gln	missense	Exon 7 of 7	NP_004919.1	O43822-1
CFAP410	NM_001271441.2		c.1119C>A	p.His373Gln	missense	Exon 7 of 7	NP_001258370.1	O43822-4
CFAP410	NM_001271440.2		c.759C>A	p.His253Gln	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.762C>A	p.His254Gln	missense	Exon 7 of 7	ENSP00000344566.4	O43822-1
CFAP410	ENST00000397956.7	TSL:1	c.1119C>A	p.His373Gln	missense	Exon 7 of 7	ENSP00000381047.3	O43822-4
CFAP410	ENST00000325223.7	TSL:1	c.759C>A	p.His253Gln	missense	Exon 7 of 7	ENSP00000317302.7	O43822-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1417438

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

702176

African (AFR)

AF:

0.00

AC:

AN:

32762

American (AMR)

AF:

0.00

AC:

AN:

39394

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25404

East Asian (EAS)

AF:

0.00

AC:

AN:

37588

South Asian (SAS)

AF:

0.00

AC:

AN:

81568

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4976

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093884

Other (OTH)

AF:

0.00

AC:

AN:

58864

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.7

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.0063

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.32

M_CAP

Benign

0.0061

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.0

PhyloP100

0.55

PROVEAN

Benign

-0.13

REVEL

Benign

0.016

Sift

Benign

0.086

Sift4G

Benign

0.26

Polyphen

0.0

Vest4

0.11

MutPred

0.10

Gain of helix (P = 0.0854)

MVP

0.25

MPC

0.29

ClinPred

0.093

GERP RS

-0.93

Varity_R

0.051

gMVP

0.026

Mutation Taster

=97/3

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