chr2-55533926-C-T

Position:

• chr2-55533926-C-T

Variant summary

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

The ENST00000349456.9(CFAP36):​c.451C>T​(p.His151Tyr) 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 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: 2.87

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=0.18851498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP36	NM_080667.7	c.451C>T	p.His151Tyr	missense_variant	5/10	ENST00000349456.9	NP_542398.3
CFAP36	NM_001282761.2	c.526C>T	p.His176Tyr	missense_variant	6/11		NP_001269690.1
CFAP36	XM_047443086.1	c.91C>T	p.His31Tyr	missense_variant	2/7		XP_047299042.1
CFAP36	XM_011532499.2	c.-9C>T		5_prime_UTR_variant	2/7		XP_011530801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP36	ENST00000349456.9	c.451C>T	p.His151Tyr	missense_variant	5/10	1	NM_080667.7	ENSP00000295117	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Jun 22, 2023

The c.451C>T (p.H151Y) alteration is located in exon 5 (coding exon 5) of the CFAP36 gene. This alteration results from a C to T substitution at nucleotide position 451, causing the histidine (H) at amino acid position 151 to be replaced by a tyrosine (Y). 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	0.095
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	.;.;T;.;T
Eigen	Benign	-0.013
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.90	D;D;D;D;D
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.2	N;N;N;N;N
REVEL	Benign	0.067
Sift	Uncertain	0.0050	D;D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D;D
Polyphen		0.098	B;.;B;.;.
Vest4		0.41
MutPred		0.27		.;Gain of phosphorylation at H151 (P = 0.005);Gain of phosphorylation at H151 (P = 0.005);Gain of phosphorylation at H151 (P = 0.005);Gain of phosphorylation at H151 (P = 0.005);
MVP		0.34
MPC		0.026
ClinPred		0.55	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.11

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: chr2-55761062;