Variant 11-102047493-A-ACTTGGG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM4BS1_Supporting

The NM_032930.3(CFAP300):c.24_29dup(p.Leu9_Gly10dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000827 in 1,535,782 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

CFAP300
NM_032930.3 inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.935

Variant links:

Genes affected

CFAP300 (HGNC:28188): (cilia and flagella associated protein 300) Predicted to be located in cytoplasm and motile cilium. Implicated in primary ciliary dyskinesia 38. [provided by Alliance of Genome Resources, Apr 2022]

CFAP300 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_032930.3.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000086 (119/1383640) while in subpopulation MID AF= 0.000878 (5/5692). AF 95% confidence interval is 0.000346. There are 0 homozygotes in gnomad4_exome. There are 58 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CFAP300	NM_032930.3 linkuse as main transcript	c.24_29dup	p.Leu9_Gly10dup	inframe_insertion	1/7	ENST00000434758.7	NP_116319.2
CFAP300	NM_001195005.2 linkuse as main transcript	c.24_29dup	p.Leu9_Gly10dup	inframe_insertion	1/4		NP_001181934.1
CFAP300	NM_001363505.2 linkuse as main transcript	c.24_29dup	p.Leu9_Gly10dup	inframe_insertion	1/6		NP_001350434.1
CFAP300	XM_005271713.5 linkuse as main transcript	c.24_29dup	p.Leu9_Gly10dup	inframe_insertion	1/6		XP_005271770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP300	ENST00000434758.7 linkuse as main transcript	c.24_29dup	p.Leu9_Gly10dup	inframe_insertion	1/7	2	NM_032930.3	ENSP00000414390	P1	Q9BRQ4-1
CFAP300	ENST00000534360.1 linkuse as main transcript	c.24_29dup	p.Leu9_Gly10dup	inframe_insertion	1/4	1		ENSP00000435482		Q9BRQ4-3
CFAP300	ENST00000530659.1 linkuse as main transcript	n.27_32dup		non_coding_transcript_exon_variant	1/6	1
CFAP300	ENST00000526781.5 linkuse as main transcript	c.24_29dup	p.Leu9_Gly10dup	inframe_insertion	1/6	3		ENSP00000433074

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

136924

Hom.:

AF XY:

0.0000672

AC XY:

AN XY:

74362

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000889

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000363

Gnomad OTH exome

AF:

0.000481

GnomAD4 exome

AF:

0.0000860

AC:

119

AN:

1383640

Hom.:

Cov.:

AF XY:

0.0000849

AC XY:

AN XY:

682780

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000202

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000871

Gnomad4 OTH exome

AF:

0.0000691

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000491

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 19, 2022

This variant, c.24_29dup, results in the insertion of 2 amino acid(s) of the C11orf70 protein (p.Leu9_Gly10dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs753634626, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with C11orf70-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over