12-54645187-T-C

Variant names:

• chr12-54645187-T-C
• NM_053283.4:c.275A>G

Variant summary

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

The NM_053283.4(DCD):​c.275A>G​(p.Glu92Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DCD NM_053283.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.180

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

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=0.12847394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCD	NM_053283.4	c.275A>G	p.Glu92Gly	missense_variant	Exon 4 of 5	ENST00000293371.11	NP_444513.1
DCD	NM_001300854.2	c.275A>G	p.Glu92Gly	missense_variant	Exon 4 of 6		NP_001287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCD	ENST00000293371.11	c.275A>G	p.Glu92Gly	missense_variant	Exon 4 of 5	1	NM_053283.4	ENSP00000293371.6
DCD	ENST00000456047.2	c.275A>G	p.Glu92Gly	missense_variant	Exon 4 of 6	1		ENSP00000406773.2
DCD	ENST00000546807.5	n.*208A>G		non_coding_transcript_exon_variant	Exon 5 of 6	1		ENSP00000450415.1
DCD	ENST00000546807.5	n.*208A>G		3_prime_UTR_variant	Exon 5 of 6	1		ENSP00000450415.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.275A>G (p.E92G) alteration is located in exon 4 (coding exon 4) of the DCD gene. This alteration results from a A to G substitution at nucleotide position 275, causing the glutamic acid (E) at amino acid position 92 to be replaced by a glycine (G). 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	0.29
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Benign	0.094
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.69	P;.
Vest4		0.15
MutPred		0.14		Loss of stability (P = 0.0212);Loss of stability (P = 0.0212);
MVP		0.17
MPC		0.11
ClinPred		0.30	T
GERP RS		1.1
Varity_R		0.45
gMVP		0.036

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: chr12-55038971;