11-102047511-T-G

Position:

• chr11-102047511-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_032930.3(CFAP300):​c.41T>G​(p.Phe14Cys) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP300 NM_032930.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.10

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 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.954

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP300	NM_032930.3	c.41T>G	p.Phe14Cys	missense_variant	1/7	ENST00000434758.7	NP_116319.2
CFAP300	NM_001363505.2	c.41T>G	p.Phe14Cys	missense_variant	1/6		NP_001350434.1
CFAP300	NM_001195005.2	c.41T>G	p.Phe14Cys	missense_variant	1/4		NP_001181934.1
CFAP300	XM_005271713.5	c.41T>G	p.Phe14Cys	missense_variant	1/6		XP_005271770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP300	ENST00000434758.7	c.41T>G	p.Phe14Cys	missense_variant	1/7	2	NM_032930.3	ENSP00000414390.2
CFAP300	ENST00000534360.1	c.41T>G	p.Phe14Cys	missense_variant	1/4	1		ENSP00000435482.1
CFAP300	ENST00000530659.1	n.44T>G		non_coding_transcript_exon_variant	1/6	1
CFAP300	ENST00000526781.5	c.41T>G	p.Phe14Cys	missense_variant	1/6	3		ENSP00000433074.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.41T>G (p.F14C) alteration is located in exon 1 (coding exon 1) of the C11orf70 gene. This alteration results from a T to G substitution at nucleotide position 41, causing the phenylalanine (F) at amino acid position 14 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;.;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Uncertain	-0.14	T
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0060	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.69
MutPred		0.89		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.27
MPC		0.30
ClinPred		0.97	D
GERP RS		4.2
Varity_R		0.37
gMVP		0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs1941895921; hg19: chr11-101918242;