20-20070852-A-G

Position:

• chr20-20070852-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_015585.4(CFAP61):​c.144-2A>G variant causes a splice acceptor, intron change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP61 NM_015585.4 splice_acceptor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.83

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 20-20070852-A-G is Pathogenic according to our data. Variant chr20-20070852-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 2504105.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr20-20070852-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP61	NM_015585.4	c.144-2A>G		splice_acceptor_variant, intron_variant		ENST00000245957.10	NP_056400.3
CFAP61	NM_001167816.1	c.144-2A>G		splice_acceptor_variant, intron_variant			NP_001161288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP61	ENST00000245957.10	c.144-2A>G		splice_acceptor_variant, intron_variant		1	NM_015585.4	ENSP00000245957.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spermatogenic failure 84 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	34
DANN	Uncertain	0.98
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.94	D
GERP RS		5.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.83
SpliceAI score (max)		0.97		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.73		Position offset: 9
DS_AL_spliceai		0.97		Position offset: 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: chr20-20051496; COSMIC: COSV55619290; COSMIC: COSV55619290;