12-54644751-C-G

Variant names:

• chr12-54644751-C-G
• rs199541255
• NM_053283.4:c.295G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_053283.4(DCD):​c.295G>C​(p.Val99Leu) 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. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V99I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 29)
• Consequence: DCD NM_053283.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 2 publications found

Genes affected

DCD (HGNC:14669): (dermcidin) This antimicrobial gene encodes a secreted protein that is subsequently processed into mature peptides of distinct biological activities. The C-terminal peptide is constitutively expressed in sweat and has antibacterial and antifungal activities. The N-terminal peptide, also known as diffusible survival evasion peptide, promotes neural cell survival under conditions of severe oxidative stress. A glycosylated form of the N-terminal peptide may be associated with cachexia (muscle wasting) in cancer patients. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07729915).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053283.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCD	NM_053283.4	MANE Select	c.295G>C	p.Val99Leu	missense	Exon 5 of 5	NP_444513.1	P81605-1
	DCD	NM_001300854.2		c.359G>C	p.Arg120Pro	missense	Exon 6 of 6	NP_001287783.1	P81605-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCD	ENST00000293371.11	TSL:1 MANE Select	c.295G>C	p.Val99Leu	missense	Exon 5 of 5	ENSP00000293371.6	P81605-1
	DCD	ENST00000456047.2	TSL:1	c.359G>C	p.Arg120Pro	missense	Exon 6 of 6	ENSP00000406773.2	P81605-2
	DCD	ENST00000546807.5	TSL:1	n.*228G>C		non_coding_transcript_exon	Exon 6 of 6	ENSP00000450415.1	P81605-3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.39
DANN	Benign	0.25
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0053	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.072
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.067
Sift	Pathogenic	0.0	D
Vest4		0.063
MutPred		0.19		Gain of glycosylation at R120 (P = 0.0131)
MVP		0.20
ClinPred		0.053	T
GERP RS		-1.8
Varity_R		0.15
gMVP		0.0087
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs199541255; hg19: chr12-55038535;