chr12-54645221-C-T

Variant names:

• chr12-54645221-C-T
• rs371634807
• NM_053283.4:c.241G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_053283.4(DCD):​c.241G>A​(p.Gly81Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000638 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000060 (0 hom.)
• Consequence: DCD NM_053283.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.39

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037628144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCD	NM_053283.4	c.241G>A	p.Gly81Arg	missense_variant	Exon 4 of 5	ENST00000293371.11	NP_444513.1
DCD	NM_001300854.2	c.241G>A	p.Gly81Arg	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.241G>A	p.Gly81Arg	missense_variant	Exon 4 of 5	1	NM_053283.4	ENSP00000293371.6
DCD	ENST00000456047.2	c.241G>A	p.Gly81Arg	missense_variant	Exon 4 of 6	1		ENSP00000406773.2
DCD	ENST00000546807.5	n.*174G>A		non_coding_transcript_exon_variant	Exon 5 of 6	1		ENSP00000450415.1
DCD	ENST00000546807.5	n.*174G>A		3_prime_UTR_variant	Exon 5 of 6	1		ENSP00000450415.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152022 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000755

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000994 AC: 25 AN: 251414 Hom.: 0 AF XY: 0.000103 AC XY: 14 AN XY: 135882

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000595 AC: 87 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.0000578 AC XY: 42 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.000187

Gnomad4 NFE exome AF: 0.0000567

Gnomad4 OTH exome AF: 0.000116

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152022 Hom.: 0 Cov.: 31 AF XY: 0.0000943 AC XY: 7 AN XY: 74240

Gnomad4 AFR AF: 0.0000725

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000755

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000114 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.000140 AC: 17

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.241G>A (p.G81R) alteration is located in exon 4 (coding exon 4) of the DCD gene. This alteration results from a G to A substitution at nucleotide position 241, causing the glycine (G) at amino acid position 81 to be replaced by an arginine (R). 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	-0.42	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.0
DANN	Benign	0.31
DEOGEN2	Benign	0.20	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.038	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.6	D;N
REVEL	Benign	0.047
Sift	Benign	0.18	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.014	B;.
Vest4		0.21
MutPred		0.25		Gain of MoRF binding (P = 0.0106);Gain of MoRF binding (P = 0.0106);
MVP		0.31
MPC		0.22
ClinPred		0.019	T
GERP RS		-4.5
Varity_R		0.27
gMVP		0.010

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: rs371634807; hg19: chr12-55039005; COSMIC: COSV53202580;