20-20228340-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015585.4(CFAP61):​c.2024G>C​(p.Ser675Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CFAP61 NM_015585.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04365599).

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>C	p.Ser675Thr	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>C	p.Ser675Thr	missense	Exon 18 of 27	ENSP00000245957.5	Q8NHU2-1
	CFAP61	ENST00000377293.5	TSL:1	c.92G>C	p.Ser31Thr	missense	Exon 2 of 6	ENSP00000366508.1	Q8NHU2-5
	CFAP61	ENST00000389656.4	TSL:1	c.92G>C	p.Ser31Thr	missense	Exon 1 of 5	ENSP00000374307.3	Q8NHU2-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459690 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725970

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110330

Other (OTH) AF: 0.00 AC: 0 AN: 60316

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.073
DANN	Benign	0.43
DEOGEN2	Benign	0.034	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.21
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.050
Sift	Benign	0.32	T
Sift4G	Benign	0.066	T
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.50		Loss of sheet (P = 0.1158)
MVP		0.15
MPC		0.10
ClinPred		0.37	T
GERP RS		-12
PromoterAI		0.0090	Neutral
Varity_R		0.056
gMVP		0.43
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;