chr19-35511468-ACCACTGCTGCCG-A

Variant names:

• chr19-35511468-ACCACTGCTGCCG-A
• rs760401945
• NM_033317.5:c.849_860delCGGCAGCAGTGG

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM4 BS1 BS2

The NM_033317.5(DMKN):​c.849_860delCGGCAGCAGTGG​(p.Gly284_Gly287del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00352 in 1,095,180 control chromosomes in the GnomAD database, including 23 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0096 (8 hom., cov: 22)
  • Exomes 𝑓: 0.0030 (15 hom.)
• Consequence: DMKN NM_033317.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 0 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 -6 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_033317.5.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00958 (806/84144) while in subpopulation AFR AF = 0.0359 (596/16618). AF 95% confidence interval is 0.0335. There are 8 homozygotes in GnomAd4. There are 392 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033317.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMKN	NM_033317.5	MANE Select	c.849_860delCGGCAGCAGTGG	p.Gly284_Gly287del	disruptive_inframe_deletion	Exon 5 of 16	NP_201574.4
	DMKN	NM_001190348.2		c.849_860delCGGCAGCAGTGG	p.Gly284_Gly287del	disruptive_inframe_deletion	Exon 5 of 13	NP_001177277.1	Q6E0U4-6
	DMKN	NM_001126057.3		c.849_860delCGGCAGCAGTGG	p.Gly284_Gly287del	disruptive_inframe_deletion	Exon 5 of 11	NP_001119529.2	Q6E0U4-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMKN	ENST00000339686.8	TSL:1 MANE Select	c.849_860delCGGCAGCAGTGG	p.Gly284_Gly287del	disruptive_inframe_deletion	Exon 5 of 16	ENSP00000342012.3	Q6E0U4-1
	DMKN	ENST00000447113.6	TSL:1	c.849_860delCGGCAGCAGTGG	p.Gly284_Gly287del	disruptive_inframe_deletion	Exon 5 of 13	ENSP00000394908.2	Q6E0U4-6
	DMKN	ENST00000424570.6	TSL:1	c.849_860delCGGCAGCAGTGG	p.Gly284_Gly287del	disruptive_inframe_deletion	Exon 5 of 11	ENSP00000388404.2	Q6E0U4-5

Frequencies

GnomAD3 genomes AF: 0.00957 AC: 805 AN: 84128 Hom.: 8 Cov.: 22

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.00147

Gnomad AMR AF: 0.00725

Gnomad ASJ AF: 0.00532

Gnomad EAS AF: 0.0292

Gnomad SAS AF: 0.00155

Gnomad FIN AF: 0.000763

Gnomad MID AF: 0.0144

Gnomad NFE AF: 0.00149

Gnomad OTH AF: 0.0103

GnomAD4 exome AF: 0.00302 AC: 3050 AN: 1011036 Hom.: 15 AF XY: 0.00297 AC XY: 1484 AN XY: 499748

African (AFR) AF: 0.0285 AC: 570 AN: 19972

American (AMR) AF: 0.00805 AC: 142 AN: 17648

Ashkenazi Jewish (ASJ) AF: 0.00458 AC: 80 AN: 17452

East Asian (EAS) AF: 0.0385 AC: 603 AN: 15670

South Asian (SAS) AF: 0.00144 AC: 73 AN: 50804

European-Finnish (FIN) AF: 0.00430 AC: 133 AN: 30952

Middle Eastern (MID) AF: 0.00278 AC: 8 AN: 2882

European-Non Finnish (NFE) AF: 0.00155 AC: 1265 AN: 814940

Other (OTH) AF: 0.00432 AC: 176 AN: 40716

GnomAD4 genome AF: 0.00958 AC: 806 AN: 84144 Hom.: 8 Cov.: 22 AF XY: 0.00958 AC XY: 392 AN XY: 40918

African (AFR) AF: 0.0359 AC: 596 AN: 16618

American (AMR) AF: 0.00725 AC: 52 AN: 7170

Ashkenazi Jewish (ASJ) AF: 0.00532 AC: 12 AN: 2256

East Asian (EAS) AF: 0.0293 AC: 55 AN: 1874

South Asian (SAS) AF: 0.00156 AC: 4 AN: 2566

European-Finnish (FIN) AF: 0.000763 AC: 5 AN: 6556

Middle Eastern (MID) AF: 0.0103 AC: 2 AN: 194

European-Non Finnish (NFE) AF: 0.00149 AC: 67 AN: 45044

Other (OTH) AF: 0.0101 AC: 12 AN: 1188

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=199/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs760401945; hg19: chr19-36002370;