20-20075497-C-T

Variant names:

• chr20-20075497-C-T
• rs1568841657
• NM_015585.4:c.448C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015585.4(CFAP61):​c.448C>T​(p.Leu150Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L150V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CFAP61 NM_015585.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99
• Publications: 0 publications found

Genes affected

CFAP61 (HGNC:15872): (cilia and flagella associated protein 61) Predicted to be involved in cilium movement and cilium organization. Predicted to be located in axoneme and motile cilium. Predicted to colocalize with radial spoke stalk. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000309008 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015585.4. 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
	CFAP61	NM_015585.4	MANE Select	c.448C>T	p.Leu150Phe	missense	Exon 6 of 27	NP_056400.3
	CFAP61	NM_001167816.1		c.448C>T	p.Leu150Phe	missense	Exon 5 of 13	NP_001161288.1	Q8NHU2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP61	ENST00000245957.10	TSL:1 MANE Select	c.448C>T	p.Leu150Phe	missense	Exon 6 of 27	ENSP00000245957.5	Q8NHU2-1
	CFAP61	ENST00000451767.6	TSL:1	c.448C>T	p.Leu150Phe	missense	Exon 5 of 13	ENSP00000414537.2	Q8NHU2-3
	CFAP61	ENST00000340348.10	TSL:1	c.310C>T	p.Leu104Phe	missense	Exon 5 of 11	ENSP00000345553.6	F8W6E2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251368 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461744 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727190

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111892

Other (OTH) AF: 0.0000166 AC: 1 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.83	T
PhyloP100		3.0
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.25
Sift	Benign	0.066	T
Sift4G	Benign	0.076	T
Polyphen		1.0	D
Vest4		0.47
MutPred		0.68		Gain of sheet (P = 0.1945)
MVP		0.59
MPC		0.57
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.12
gMVP		0.47
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1568841657; hg19: chr20-20056141;