3-48223630-T-C

Variant summary

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

The NM_004345.5(CAMP):c.119T>C(p.Leu40Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAMP NM_004345.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.559

Genes affected

CAMP (HGNC:1472): (cathelicidin antimicrobial peptide) This gene encodes a member of an antimicrobial peptide family, characterized by a highly conserved N-terminal signal peptide containing a cathelin domain and a structurally variable cationic antimicrobial peptide, which is produced by extracellular proteolysis from the C-terminus. The protein plays an important role in innate immunity defense against viruses. In addition to its antibacterial, antifungal, and antiviral activities, the encoded protein functions in cell chemotaxis, immune mediator induction, and inflammatory response regulation. [provided by RefSeq, Sep 2021]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMP	NM_004345.5	c.119T>C	p.Leu40Pro	missense_variant	1/4	ENST00000652295.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMP	ENST00000652295.2	c.119T>C	p.Leu40Pro	missense_variant	1/4		NM_004345.5	A2
CAMP	ENST00000296435.2	c.128T>C	p.Leu43Pro	missense_variant	1/4	1		P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jul 19, 2022

The c.128T>C (p.L43P) alteration is located in exon 1 (coding exon 1) of the CAMP gene. This alteration results from a T to C substitution at nucleotide position 128, causing the leucine (L) at amino acid position 43 to be replaced by a proline (P). 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	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
Cadd	Benign	21
Dann	Uncertain	0.99
Eigen	Benign	-0.030
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.069	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0046	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.51	T
REVEL	Benign	0.21
Sift4G	Benign	0.075	T
Vest4		0.79
MVP		0.80
MPC		0.46
ClinPred		0.46	T
GERP RS		2.2
gMVP		0.74

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: chr3-48265120;