19-35507460-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000419602.5(DMKN):​c.943A>T​(p.Arg315Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,550,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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 0.00015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: DMKN ENST00000419602.5 missense, splice_region
• Scores: Splicing: ADA: 0.0003139
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08202368).

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>T		intron	N/A	NP_201574.4
	DMKN	NM_001126056.3		c.943A>T	p.Arg315Trp	missense splice_region	Exon 8 of 18	NP_001119528.3
	DMKN	NM_001190348.2		c.1126A>T	p.Arg376Trp	missense splice_region	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>T	p.Arg315Trp	missense splice_region	Exon 8 of 18	ENSP00000391036.1
	DMKN	ENST00000447113.6	TSL:1	c.1126A>T	p.Arg376Trp	missense splice_region	Exon 9 of 13	ENSP00000394908.2
	DMKN	ENST00000434389.5	TSL:1	c.166A>T	p.Arg56Trp	missense splice_region	Exon 4 of 14	ENSP00000388378.1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 151912 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000484

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: 0.000284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000141 AC: 22 AN: 156358 AF XY: 0.000145

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000238

Gnomad NFE exome AF: 0.000298

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000184 AC: 257 AN: 1399032 Hom.: 0 Cov.: 33 AF XY: 0.000174 AC XY: 120 AN XY: 690058

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.00 AC: 0 AN: 79222

European-Finnish (FIN) AF: 0.000264 AC: 13 AN: 49216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.000219 AC: 236 AN: 1078712

Other (OTH) AF: 0.000138 AC: 8 AN: 57990

GnomAD4 genome AF: 0.000151 AC: 23 AN: 151912 Hom.: 0 Cov.: 31 AF XY: 0.000216 AC XY: 16 AN XY: 74168

African (AFR) AF: 0.0000484 AC: 2 AN: 41332

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.000284 AC: 3 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67954

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000271 Hom.: 3247

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.0000777 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Uncertain	1.0
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.1
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.056
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.030	D
Polyphen		0.76	P
Vest4		0.19
MVP		0.22
ClinPred		0.16	T
GERP RS		3.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00031
dbscSNV1_RF	Benign	0.026

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

Other links and lift over

dbSNP: rs4254439; hg19: chr19-35998362;