19-35507460-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000419602.5(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 ENST00000419602.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.0002806
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000419602.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMKN	NM_033317.5	MANE Select	c.1039-1474A>C		intron	N/A	NP_201574.4
	DMKN	NM_001126056.3		c.943A>C	p.Arg315Arg	splice_region synonymous	Exon 8 of 18	NP_001119528.3
	DMKN	NM_001190348.2		c.1126A>C	p.Arg376Arg	splice_region synonymous	Exon 9 of 13	NP_001177277.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMKN	ENST00000419602.5	TSL:1	c.943A>C	p.Arg315Arg	splice_region synonymous	Exon 8 of 18	ENSP00000391036.1
	DMKN	ENST00000447113.6	TSL:1	c.1126A>C	p.Arg376Arg	splice_region synonymous	Exon 9 of 13	ENSP00000394908.2
	DMKN	ENST00000434389.5	TSL:1	c.166A>C	p.Arg56Arg	splice_region synonymous	Exon 4 of 14	ENSP00000388378.1

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

GnomAD2 exomes AF: 0.338 AC: 52905 AN: 156358 AF XY: 0.335

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 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

African (AFR) AF: 0.407 AC: 12836 AN: 31570

American (AMR) AF: 0.345 AC: 12305 AN: 35692

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 7767 AN: 25168

East Asian (EAS) AF: 0.456 AC: 16280 AN: 35706

South Asian (SAS) AF: 0.370 AC: 29316 AN: 79188

European-Finnish (FIN) AF: 0.397 AC: 19556 AN: 49204

Middle Eastern (MID) AF: 0.320 AC: 1822 AN: 5698

European-Non Finnish (NFE) AF: 0.291 AC: 313376 AN: 1078236

Other (OTH) AF: 0.316 AC: 18312 AN: 57956

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

African (AFR) AF: 0.408 AC: 16888 AN: 41434

American (AMR) AF: 0.317 AC: 4848 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3470

East Asian (EAS) AF: 0.435 AC: 2244 AN: 5156

South Asian (SAS) AF: 0.366 AC: 1764 AN: 4814

European-Finnish (FIN) AF: 0.391 AC: 4132 AN: 10568

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19718 AN: 67934

Other (OTH) AF: 0.326 AC: 690 AN: 2116

Alfa AF: 0.285 Hom.: 3247

Bravo AF: 0.339

Asia WGS AF: 0.373 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		2.1
Mutation Taster		=83/17	polymorphism (auto)

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

Other links and lift over

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