20-20228340-G-T

Variant names:

• chr20-20228340-G-T
• rs34744783
• NM_015585.4:c.2024G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015585.4(CFAP61):​c.2024G>T​(p.Ser675Ile) variant causes a missense 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CFAP61 NM_015585.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• Publications: 2 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10250932).

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.2024G>T	p.Ser675Ile	missense	Exon 18 of 27	NP_056400.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP61	ENST00000245957.10	TSL:1 MANE Select	c.2024G>T	p.Ser675Ile	missense	Exon 18 of 27	ENSP00000245957.5	Q8NHU2-1
	CFAP61	ENST00000377293.5	TSL:1	c.92G>T	p.Ser31Ile	missense	Exon 2 of 6	ENSP00000366508.1	Q8NHU2-5
	CFAP61	ENST00000389656.4	TSL:1	c.92G>T	p.Ser31Ile	missense	Exon 1 of 5	ENSP00000374307.3	Q8NHU2-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.21
DANN	Benign	0.92
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.21
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.60	P
Vest4		0.26
MutPred		0.55		Gain of catalytic residue at S675 (P = 0.1947)
MVP		0.15
MPC		0.15
ClinPred		0.58	D
GERP RS		-12
PromoterAI		0.023	Neutral
Varity_R		0.21
gMVP		0.59
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs34744783; hg19: chr20-20208984;