20-20263043-G-T

Variant names:

• chr20-20263043-G-T
• rs1288236210
• NM_015585.4:c.2416G>T

Variant summary

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

The NM_015585.4(CFAP61):​c.2416G>T​(p.Val806Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CFAP61 NM_015585.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72
• 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]

CFAP61-AS1 (HGNC:40731): (CFAP61 antisense RNA 1)

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.2416G>T	p.Val806Phe	missense	Exon 21 of 27	NP_056400.3
	CFAP61-AS1	NR_183978.1		n.345-3247C>A		intron	N/A
	CFAP61-AS1	NR_183979.1		n.345-3247C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP61	ENST00000245957.10	TSL:1 MANE Select	c.2416G>T	p.Val806Phe	missense	Exon 21 of 27	ENSP00000245957.5	Q8NHU2-1
	CFAP61	ENST00000377293.5	TSL:1	c.484G>T	p.Val162Phe	missense	Exon 5 of 6	ENSP00000366508.1	Q8NHU2-5
	CFAP61	ENST00000389656.4	TSL:1	c.484G>T	p.Val162Phe	missense	Exon 4 of 5	ENSP00000374307.3	Q8NHU2-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461808 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727216

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111944

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.7
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.14
Sift	Benign	0.059	T
Sift4G	Benign	0.11	T
Polyphen		0.96	D
Vest4		0.60
MutPred		0.38		Loss of ubiquitination at K805 (P = 0.0573)
MVP		0.29
MPC		0.30
ClinPred		0.57	D
GERP RS		2.1
Varity_R		0.14
gMVP		0.83
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1288236210; hg19: chr20-20243687;