Variant chr2-55544328-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000349456.9(CFAP36):c.886C>G(p.Gln296Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000917 in 1,613,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

CFAP36
ENST00000349456.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.582

Variant links:

Genes affected

CFAP36 (HGNC:30540): (cilia and flagella associated protein 36) Enables protein N-terminus binding activity. Located in ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

CFAP36 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0397619).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CFAP36	NM_080667.7 linkuse as main transcript	c.886C>G	p.Gln296Glu	missense_variant	9/10	ENST00000349456.9	NP_542398.3
CFAP36	NM_001282761.2 linkuse as main transcript	c.961C>G	p.Gln321Glu	missense_variant	10/11		NP_001269690.1
CFAP36	XM_047443086.1 linkuse as main transcript	c.526C>G	p.Gln176Glu	missense_variant	6/7		XP_047299042.1
CFAP36	XM_011532499.2 linkuse as main transcript	c.427C>G	p.Gln143Glu	missense_variant	6/7		XP_011530801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP36	ENST00000349456.9 linkuse as main transcript	c.886C>G	p.Gln296Glu	missense_variant	9/10	1	NM_080667.7	ENSP00000295117	P1	Q96G28-1

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

151968

Hom.:

Cov.:

show subpopulations

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:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000112

AC:

AN:

250632

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135458

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:

0.00

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.0000924

AC:

135

AN:

1461404

Hom.:

Cov.:

AF XY:

0.0000949

AC XY:

AN XY:

726958

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:

0.00

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.0000953

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000855

AC:

AN:

151968

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000140

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.886C>G (p.Q296E) alteration is located in exon 9 (coding exon 9) of the CFAP36 gene. This alteration results from a C to G substitution at nucleotide position 886, causing the glutamine (Q) at amino acid position 296 to be replaced by a glutamic acid (E). 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

0.064

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.26

DANN

Benign

0.62

DEOGEN2

Benign

0.011

.;T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.65

T;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.040

T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.39

N;N;N

REVEL

Benign

0.072

Sift

Benign

0.60

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.17

MVP

0.22

MPC

0.023

ClinPred

0.042

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.070

gMVP

0.048

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

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