chr2-55533931-A-C

Position:

• chr2-55533931-A-C

Variant summary

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

The ENST00000349456.9(CFAP36):​c.456A>C​(p.Glu152Asp) 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: 2.32

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=0.1842725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP36	NM_080667.7	c.456A>C	p.Glu152Asp	missense_variant	5/10	ENST00000349456.9	NP_542398.3
CFAP36	NM_001282761.2	c.531A>C	p.Glu177Asp	missense_variant	6/11		NP_001269690.1
CFAP36	XM_047443086.1	c.96A>C	p.Glu32Asp	missense_variant	2/7		XP_047299042.1
CFAP36	XM_011532499.2	c.-4A>C		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.456A>C	p.Glu152Asp	missense_variant	5/10	1	NM_080667.7	ENSP00000295117	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

Dec 14, 2023

The c.456A>C (p.E152D) alteration is located in exon 5 (coding exon 5) of the CFAP36 gene. This alteration results from a A to C substitution at nucleotide position 456, causing the glutamic acid (E) at amino acid position 152 to be replaced by an aspartic acid (D). 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	0.28
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	.;.;T;.;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	0.75	D;D;D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.77	N;N;N;N;N
REVEL	Benign	0.089
Sift	Uncertain	0.018	D;T;D;D;T
Sift4G	Benign	0.18	T;T;T;T;T
Polyphen		0.95	P;.;B;.;.
Vest4		0.45
MutPred		0.16		.;Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP		0.48
MPC		0.029
ClinPred		0.89	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.24

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: rs1684416642; hg19: chr2-55761067;