NM_033317.5:c.850G>T

Variant names:

• chr19-35511479-C-A
• rs12981076
• NM_033317.5:c.850G>T

Variant summary

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

The NM_033317.5(DMKN):​c.850G>T​(p.Gly284Cys) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DMKN NM_033317.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.40

Genes affected

DMKN (HGNC:25063): (dermokine) This gene is upregulated in inflammatory diseases, and it was first observed as expressed in the differentiated layers of skin. The most interesting aspect of this gene is the differential use of promoters and terminators to generate isoforms with unique cellular distributions and domain components. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2010]

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=0.13148066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMKN	NM_033317.5	c.850G>T	p.Gly284Cys	missense_variant	Exon 5 of 16	ENST00000339686.8	NP_201574.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMKN	ENST00000339686.8	c.850G>T	p.Gly284Cys	missense_variant	Exon 5 of 16	1	NM_033317.5	ENSP00000342012.3

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000117 AC: 1 AN: 851506 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 424914

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: 0.00000150

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.1
DANN	Benign	0.92
DEOGEN2	Benign	0.0082	T;.;.;.;.
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.26	T;T;T;T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.0	L;L;L;L;L
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.6	D;D;D;D;N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Uncertain	0.056	T;D;T;D;D
Polyphen		0.99	D;.;P;P;P
Vest4		0.27
MutPred		0.28		Gain of glycosylation at S282 (P = 0.1079);Gain of glycosylation at S282 (P = 0.1079);Gain of glycosylation at S282 (P = 0.1079);Gain of glycosylation at S282 (P = 0.1079);Gain of glycosylation at S282 (P = 0.1079);
MVP		0.067
MPC		0.071
ClinPred		0.66	D
GERP RS		-3.4
Varity_R		0.27
gMVP		0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12981076; hg19: chr19-36002381;