chr2-55535753-G-C

Position:

• chr2-55535753-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000349456.9(CFAP36):​c.527G>C​(p.Arg176Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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)
• Consequence: CFAP36 ENST00000349456.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.63

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18576238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP36	NM_080667.7	c.527G>C	p.Arg176Thr	missense_variant	6/10	ENST00000349456.9	NP_542398.3
CFAP36	NM_001282761.2	c.602G>C	p.Arg201Thr	missense_variant	7/11		NP_001269690.1
CFAP36	XM_047443086.1	c.167G>C	p.Arg56Thr	missense_variant	3/7		XP_047299042.1
CFAP36	XM_011532499.2	c.68G>C	p.Arg23Thr	missense_variant	3/7		XP_011530801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP36	ENST00000349456.9	c.527G>C	p.Arg176Thr	missense_variant	6/10	1	NM_080667.7	ENSP00000295117	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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 27, 2022

The c.527G>C (p.R176T) alteration is located in exon 6 (coding exon 6) of the CFAP36 gene. This alteration results from a G to C substitution at nucleotide position 527, causing the arginine (R) at amino acid position 176 to be replaced by a threonine (T). 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	0.16
BayesDel_addAF	Benign	-0.00067	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.027	.;.;T;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	D;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.2	N;N;N;N;N
REVEL	Benign	0.074
Sift	Benign	0.057	T;D;D;T;D
Sift4G	Uncertain	0.057	T;D;T;D;D
Polyphen		0.99	D;.;P;.;.
Vest4		0.29
MutPred		0.27		.;Gain of phosphorylation at R176 (P = 0.0047);Gain of phosphorylation at R176 (P = 0.0047);Gain of phosphorylation at R176 (P = 0.0047);Gain of phosphorylation at R176 (P = 0.0047);
MVP		0.63
MPC		0.028
ClinPred		0.66	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.087
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-55762889;