19-35507460-T-G

Variant names:

• chr19-35507460-T-G
• rs4254439
• ENST00000419602.5:c.943A>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001126056.3(DMKN):​c.943A>C​(p.Arg315Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,550,390 control chromosomes in the GnomAD database, including 76,756 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (8989 hom., cov: 31)
  • Exomes 𝑓: 0.31 (67767 hom.)
• Consequence: DMKN NM_001126056.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.0002806
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=2.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMKN	NM_033317.5	c.1039-1474A>C		intron_variant	Intron 7 of 15	ENST00000339686.8	NP_201574.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMKN	ENST00000339686.8	c.1039-1474A>C		intron_variant	Intron 7 of 15	1	NM_033317.5	ENSP00000342012.3

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51558 AN: 151854 Hom.: 8987 Cov.: 31

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.325

GnomAD3 exomes AF: 0.338 AC: 52905 AN: 156358 Hom.: 9064 AF XY: 0.335 AC XY: 27788 AN XY: 82872

Gnomad AFR exome AF: 0.410

Gnomad AMR exome AF: 0.348

Gnomad ASJ exome AF: 0.309

Gnomad EAS exome AF: 0.426

Gnomad SAS exome AF: 0.368

Gnomad FIN exome AF: 0.393

Gnomad NFE exome AF: 0.289

Gnomad OTH exome AF: 0.305

GnomAD4 exome AF: 0.309 AC: 431570 AN: 1398418 Hom.: 67767 Cov.: 33 AF XY: 0.310 AC XY: 213582 AN XY: 689796

Gnomad4 AFR exome AF: 0.407

Gnomad4 AMR exome AF: 0.345

Gnomad4 ASJ exome AF: 0.309

Gnomad4 EAS exome AF: 0.456

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.397

Gnomad4 NFE exome AF: 0.291

Gnomad4 OTH exome AF: 0.316

GnomAD4 genome AF: 0.340 AC: 51611 AN: 151972 Hom.: 8989 Cov.: 31 AF XY: 0.343 AC XY: 25504 AN XY: 74260

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.326

Alfa AF: 0.279 Hom.: 2658

Bravo AF: 0.339

Asia WGS AF: 0.373 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00028
dbscSNV1_RF	Benign	0.020

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

Publications

LitVar

Other links and lift over

dbSNP: rs4254439; hg19: chr19-35998362; COSMIC: COSV60085106; COSMIC: COSV60085106;