20-20191344-T-G

Variant names:

• chr20-20191344-T-G
• rs7344530
• NM_015585.4:c.1515T>G

Variant summary

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

The NM_015585.4(CFAP61):​c.1515T>G​(p.Asp505Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. D505N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP61 NM_015585.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 3 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 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.1515T>G	p.Asp505Glu	missense_variant, splice_region_variant	Exon 15 of 27	ENST00000245957.10	NP_056400.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP61	ENST00000245957.10	c.1515T>G	p.Asp505Glu	missense_variant, splice_region_variant	Exon 15 of 27	1	NM_015585.4	ENSP00000245957.5
CFAP61	ENST00000674269.1	c.1512+3288T>G		intron_variant	Intron 14 of 17			ENSP00000501498.1
CFAP61	ENST00000431753.1	c.207+3288T>G		intron_variant	Intron 2 of 4	5		ENSP00000388074.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.050
Eigen_PC	Benign	-0.023
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.3
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.090
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.0040	D
Vest4		0.068
ClinPred		0.91	D
GERP RS		2.1
Varity_R		0.13
gMVP		0.44
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.23		Position offset: -2

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

Other links and lift over

dbSNP: rs7344530; hg19: chr20-20171988;