21-32612147-G-A

Variant names:

• chr21-32612147-G-A
• rs753786167
• NM_021254.4:c.97C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001350334.2(CFAP298):​c.-133C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,577,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: CFAP298 NM_001350334.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29031724).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350334.2. 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.97C>T	p.Arg33Trp	missense	Exon 1 of 7	NP_067077.1	P57076
	CFAP298	NM_001350334.2		c.-133C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001337263.1
	CFAP298-TCP10L	NM_001350338.2		c.97C>T	p.Arg33Trp	missense	Exon 1 of 8	NP_001337267.1	A0A669KAY3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP298	ENST00000290155.8	TSL:1 MANE Select	c.97C>T	p.Arg33Trp	missense	Exon 1 of 7	ENSP00000290155.3	P57076
	CFAP298-TCP10L	ENST00000673807.1		c.97C>T	p.Arg33Trp	missense	Exon 1 of 8	ENSP00000501088.1	A0A669KAY3
	CFAP298	ENST00000382549.8	TSL:1	c.97C>T	p.Arg33Trp	missense	Exon 1 of 5	ENSP00000371989.4	D3DSE6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000213 AC: 4 AN: 187758 AF XY: 0.00000990

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000106

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000126 AC: 18 AN: 1425336 Hom.: 0 Cov.: 31 AF XY: 0.0000142 AC XY: 10 AN XY: 705514

African (AFR) AF: 0.00 AC: 0 AN: 32758

American (AMR) AF: 0.0000509 AC: 2 AN: 39256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25408

East Asian (EAS) AF: 0.00 AC: 0 AN: 37780

South Asian (SAS) AF: 0.0000247 AC: 2 AN: 81126

European-Finnish (FIN) AF: 0.0000400 AC: 2 AN: 49938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.0000101 AC: 11 AN: 1094202

Other (OTH) AF: 0.0000169 AC: 1 AN: 59148

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74360

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.00000832 AC: 1

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	0.12
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.093
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.088	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.99	T
PhyloP100		1.2
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.13
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.017	D
Polyphen		0.95	P
Vest4		0.52
MutPred		0.49		Gain of catalytic residue at A32 (P = 0.025)
MVP		0.35
MPC		0.25
ClinPred		0.80	D
GERP RS		3.9
PromoterAI		0.0044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.18
gMVP		0.42
Mutation Taster		=87/13	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: rs753786167; hg19: chr21-33984457;