rs878855068

Variant names:

• chr21-32609895-C-T
• rs878855068
• NM_021254.4:c.250G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-32609895-C-T
• chr21-32609895-C-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021254.4(CFAP298):​c.250G>A​(p.Val84Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: CFAP298 NM_021254.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.244
• Publications: 4 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024341792).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP298	NM_021254.4	MANE Select	c.250G>A	p.Val84Ile	missense	Exon 2 of 7	NP_067077.1	P57076
	CFAP298-TCP10L	NM_001350338.2		c.250G>A	p.Val84Ile	missense	Exon 2 of 8	NP_001337267.1	A0A669KAY3
	CFAP298	NM_001350337.2		c.250G>A	p.Val84Ile	missense	Exon 2 of 6	NP_001337266.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP298	ENST00000290155.8	TSL:1 MANE Select	c.250G>A	p.Val84Ile	missense	Exon 2 of 7	ENSP00000290155.3	P57076
	CFAP298-TCP10L	ENST00000673807.1		c.250G>A	p.Val84Ile	missense	Exon 2 of 8	ENSP00000501088.1	A0A669KAY3
	CFAP298	ENST00000382549.8	TSL:1	c.250G>A	p.Val84Ile	missense	Exon 2 of 5	ENSP00000371989.4	D3DSE6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000246 AC: 36 AN: 1461832 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000306 AC: 34 AN: 1111968

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.62
DANN	Benign	0.76
DEOGEN2	Benign	0.0064	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.24
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.038
Sift	Benign	0.71	T
Sift4G	Benign	0.86	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.25		Loss of ubiquitination at K82 (P = 0.1486)
MVP		0.030
MPC		0.11
ClinPred		0.026	T
GERP RS		-8.1
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.013
gMVP		0.15
Mutation Taster		=94/6	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: rs878855068; hg19: chr21-33982205; COSMIC: COSV51591716;