rs1057518441

Variant names:

• chr21-44333224-C-T
• rs1057518441
• NM_004928.3:c.182G>A
• CFAP410 p.Cys61Tyr

Your query was ambiguous. Multiple possible variants found:

• chr21-44333224-C-T
• chr21-44333224-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004928.3(CFAP410):​c.182G>A​(p.Cys61Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. C61G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CFAP410 NM_004928.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 7.18
• Publications: 2 publications found

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
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• amyotrophic lateral sclerosis

  Inheritance: SD, AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet

ENSG00000184441 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.924

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP410	NM_004928.3	MANE Select	c.182G>A	p.Cys61Tyr	missense	Exon 4 of 7	NP_004919.1	O43822-1
	CFAP410	NM_001271441.2		c.182G>A	p.Cys61Tyr	missense	Exon 4 of 7	NP_001258370.1	O43822-4
	CFAP410	NM_001271440.2		c.182G>A	p.Cys61Tyr	missense	Exon 4 of 7	NP_001258369.1	O43822-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP410	ENST00000339818.9	TSL:1 MANE Select	c.182G>A	p.Cys61Tyr	missense	Exon 4 of 7	ENSP00000344566.4	O43822-1
	CFAP410	ENST00000397956.7	TSL:1	c.182G>A	p.Cys61Tyr	missense	Exon 4 of 7	ENSP00000381047.3	O43822-4
	CFAP410	ENST00000325223.7	TSL:1	c.182G>A	p.Cys61Tyr	missense	Exon 4 of 7	ENSP00000317302.7	O43822-3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460412 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726448

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111826

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)
1	-	-	Retinal dystrophy with or without macular staphyloma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.090	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.84	T
PhyloP100		7.2
PROVEAN	Pathogenic	-11	D
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.96
gMVP		0.75
Mutation Taster		=1/99	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1057518441;

hg19: chr21-45753107;