NM_021254.4:c.651C>G

Variant names:

• chr21-32603176-G-C
• rs200260201
• NM_021254.4:c.651C>G

Variant summary

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

The NM_021254.4(CFAP298):​c.651C>G​(p.Ile217Met) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I217I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP298 NM_021254.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• Publications: 0 publications found

Genes affected

CFAP298 (HGNC:1301): (cilia and flagella associated protein 298) This gene encodes a protein that plays a critical role in dynein arm assembly and motile cilia function. Mutations in this gene result in primary ciliary dyskinesia. Naturally occuring readthrough transcription occurs from this locus to the downstream t-complex 10 like (TCP10L) gene. [provided by RefSeq, Apr 2017]

CFAP298-TCP10L (HGNC:54636): (CFAP298-TCP10L readthrough) This locus represents naturally occurring readthrough transcription between the neighboring chromosome 21 open reading frame 59 (C21orf59) and TCP10L (t-complex 10 like) genes on chromosome 21. Readthrough transcripts may encode a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]

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=0.21847877).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021254.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP298	NM_021254.4	MANE Select	c.651C>G	p.Ile217Met	missense	Exon 5 of 7	NP_067077.1
	CFAP298-TCP10L	NM_001350338.2		c.651C>G	p.Ile217Met	missense	Exon 5 of 8	NP_001337267.1
	CFAP298	NM_001350337.2		c.651C>G	p.Ile217Met	missense	Exon 5 of 6	NP_001337266.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP298	ENST00000290155.8	TSL:1 MANE Select	c.651C>G	p.Ile217Met	missense	Exon 5 of 7	ENSP00000290155.3
	CFAP298-TCP10L	ENST00000673807.1		c.651C>G	p.Ile217Met	missense	Exon 5 of 8	ENSP00000501088.1
	CFAP298	ENST00000382549.8	TSL:1	c.651C>G	p.Ile217Met	missense	Exon 5 of 5	ENSP00000371989.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.37	T
PhyloP100		-0.20
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.23
Sift	Benign	0.034	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.99	D
Vest4		0.67
MutPred		0.30		Loss of sheet (P = 0.0126)
MVP		0.14
MPC		0.62
ClinPred		0.92	D
GERP RS		-2.1
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.83
gMVP		0.47
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs200260201; hg19: chr21-33975486;