20-20263095-T-G

Variant names:

• chr20-20263095-T-G
• NM_015585.4:c.2468T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015585.4(CFAP61):​c.2468T>G​(p.Leu823Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP61 NM_015585.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.502

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP61	NM_015585.4	c.2468T>G	p.Leu823Arg	missense_variant	Exon 21 of 27	ENST00000245957.10	NP_056400.3
CFAP61-AS1	NR_183978.1	n.345-3299A>C		intron_variant	Intron 1 of 3
CFAP61-AS1	NR_183979.1	n.345-3299A>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP61	ENST00000245957.10	c.2468T>G	p.Leu823Arg	missense_variant	Exon 21 of 27	1	NM_015585.4	ENSP00000245957.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2468T>G (p.L823R) alteration is located in exon 21 (coding exon 20) of the CFAP61 gene. This alteration results from a T to G substitution at nucleotide position 2468, causing the leucine (L) at amino acid position 823 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.76
DEOGEN2	Benign	0.063	T;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.61	T;.;T
M_CAP	Benign	0.0083	T
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Benign	-1.1	T
PROVEAN	Uncertain	-2.4	N;D;D
REVEL	Benign	0.27
Sift	Benign	0.22	T;T;T
Sift4G	Benign	0.39	T;T;T
Polyphen		0.97	D;B;B
Vest4		0.73
MutPred		0.67		Loss of stability (P = 0.063);.;.;
MVP		0.30
MPC		0.47
ClinPred		0.21	T
GERP RS		4.0
Varity_R		0.23
gMVP		0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-20243739;