chr12-113155413-G-C

Position:

• chr12-113155413-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001144872.3(CFAP73):​c.844G>C​(p.Glu282Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000931 in 1,396,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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: 0.0000093 (0 hom.)
• Consequence: CFAP73 NM_001144872.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.74

Genes affected

CFAP73 (HGNC:37100): (cilia and flagella associated protein 73) Predicted to enable dynein complex binding activity. Predicted to be involved in cilium movement and inner dynein arm assembly. Predicted to be located in axonemal outer doublet and motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30600405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP73	NM_001144872.3	c.844G>C	p.Glu282Gln	missense_variant	6/8	ENST00000335621.11
CFAP73	XM_011538327.3	c.844G>C	p.Glu282Gln	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP73	ENST00000335621.11	c.844G>C	p.Glu282Gln	missense_variant	6/8	5	NM_001144872.3	P1
CFAP73	ENST00000550918.1	c.334G>C	p.Glu112Gln	missense_variant	2/3	3
CFAP73	ENST00000551256.1	n.789G>C		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000931 AC: 13 AN: 1396434 Hom.: 0 Cov.: 31 AF XY: 0.0000131 AC XY: 9 AN XY: 688214

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000743

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000314 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.844G>C (p.E282Q) alteration is located in exon 6 (coding exon 6) of the CFAP73 gene. This alteration results from a G to C substitution at nucleotide position 844, causing the glutamic acid (E) at amino acid position 282 to be replaced by a glutamine (Q). 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	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	-0.20	T
MutationTaster	Benign	0.92	D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.17
Sift	Benign	0.031	D
Sift4G	Uncertain	0.041	D
Polyphen		1.0	D
Vest4		0.15
MutPred		0.26		Loss of ubiquitination at K285 (P = 0.0935);
MVP		0.17
ClinPred		0.96	D
GERP RS		3.8
Varity_R		0.26
gMVP		0.17

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: rs1026141733; hg19: chr12-113593218;