12-54644751-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_053283.4(DCD):​c.295G>A​(p.Val99Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000318 in 1,604,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

DCD
NM_053283.4 missense

Scores

1
14

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0720
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.039604962).
BP6
Variant 12-54644751-C-T is Benign according to our data. Variant chr12-54644751-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2331765.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DCDNM_053283.4 linkc.295G>A p.Val99Ile missense_variant Exon 5 of 5 ENST00000293371.11 NP_444513.1 P81605-1
DCDNM_001300854.2 linkc.359G>A p.Arg120His missense_variant Exon 6 of 6 NP_001287783.1 P81605-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DCDENST00000293371.11 linkc.295G>A p.Val99Ile missense_variant Exon 5 of 5 1 NM_053283.4 ENSP00000293371.6 P81605-1
DCDENST00000456047.2 linkc.359G>A p.Arg120His missense_variant Exon 6 of 6 1 ENSP00000406773.2 P81605-2
DCDENST00000546807.5 linkn.*228G>A non_coding_transcript_exon_variant Exon 6 of 6 1 ENSP00000450415.1 P81605-3
DCDENST00000546807.5 linkn.*228G>A 3_prime_UTR_variant Exon 6 of 6 1 ENSP00000450415.1 P81605-3

Frequencies

GnomAD3 genomes
AF:
0.0000402
AC:
6
AN:
149240
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.0000249
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000670
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000591
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000626
AC:
15
AN:
239750
Hom.:
0
AF XY:
0.0000773
AC XY:
10
AN XY:
129372
show subpopulations
Gnomad AFR exome
AF:
0.0000663
Gnomad AMR exome
AF:
0.000207
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000555
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000562
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000309
AC:
45
AN:
1455044
Hom.:
0
Cov.:
33
AF XY:
0.0000387
AC XY:
28
AN XY:
723250
show subpopulations
Gnomad4 AFR exome
AF:
0.0000599
Gnomad4 AMR exome
AF:
0.000181
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.0000234
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000190
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000402
AC:
6
AN:
149350
Hom.:
0
Cov.:
29
AF XY:
0.0000413
AC XY:
3
AN XY:
72706
show subpopulations
Gnomad4 AFR
AF:
0.0000249
Gnomad4 AMR
AF:
0.0000669
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000591
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000345
Hom.:
0
Bravo
AF:
0.0000718
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jan 10, 2022
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
0.32
DANN
Benign
0.41
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.000080
N
LIST_S2
Benign
0.47
T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.040
T
MetaSVM
Benign
-1.0
T
PROVEAN
Benign
-0.19
N
REVEL
Benign
0.050
Sift
Pathogenic
0.0
D
Vest4
0.059
MVP
0.11
ClinPred
0.0067
T
GERP RS
-1.8
gMVP
0.0048

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199541255; hg19: chr12-55038535; API