19-35511468-ACCACTGCTGCCGCCACTGCTGCCG-ACCACTGCTGCCGCCACTGCTGCCGCCACTGCTGCCGCCACTGCTGCCG

Variant names:

• chr19-35511468-A-ACCACTGCTGCCGCCACTGCTGCCG
• rs760401945
• NM_033317.5:c.837_860dupCGGCAGCAGTGGCGGCAGCAGTGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_033317.5(DMKN):​c.837_860dupCGGCAGCAGTGGCGGCAGCAGTGG​(p.Gly287_Gly288insGlySerSerGlyGlySerSerGly) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000238 in 84,158 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_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 0.000024 (0 hom., cov: 22)
  • Exomes 𝑓: 0.000031 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DMKN NM_033317.5 disruptive_inframe_insertion
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_033317.5.

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.837_860dupCGGCAGCAGTGGCGGCAGCAGTGG	p.Gly287_Gly288insGlySerSerGlyGlySerSerGly	disruptive_inframe_insertion	Exon 5 of 16	NP_201574.4
	DMKN	NM_001190348.2		c.837_860dupCGGCAGCAGTGGCGGCAGCAGTGG	p.Gly287_Gly288insGlySerSerGlyGlySerSerGly	disruptive_inframe_insertion	Exon 5 of 13	NP_001177277.1	Q6E0U4-6
	DMKN	NM_001126057.3		c.837_860dupCGGCAGCAGTGGCGGCAGCAGTGG	p.Gly287_Gly288insGlySerSerGlyGlySerSerGly	disruptive_inframe_insertion	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.837_860dupCGGCAGCAGTGGCGGCAGCAGTGG	p.Gly287_Gly288insGlySerSerGlyGlySerSerGly	disruptive_inframe_insertion	Exon 5 of 16	ENSP00000342012.3	Q6E0U4-1
	DMKN	ENST00000447113.6	TSL:1	c.837_860dupCGGCAGCAGTGGCGGCAGCAGTGG	p.Gly287_Gly288insGlySerSerGlyGlySerSerGly	disruptive_inframe_insertion	Exon 5 of 13	ENSP00000394908.2	Q6E0U4-6
	DMKN	ENST00000424570.6	TSL:1	c.837_860dupCGGCAGCAGTGGCGGCAGCAGTGG	p.Gly287_Gly288insGlySerSerGlyGlySerSerGly	disruptive_inframe_insertion	Exon 5 of 11	ENSP00000388404.2	Q6E0U4-5

Frequencies

GnomAD3 genomes AF: 0.0000238 AC: 2 AN: 84158 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000602

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000139

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000306 AC: 31 AN: 1011784 Hom.: 0 Cov.: 29 AF XY: 0.0000300 AC XY: 15 AN XY: 500146

African (AFR) AF: 0.000150 AC: 3 AN: 19992

American (AMR) AF: 0.00 AC: 0 AN: 17692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17456

East Asian (EAS) AF: 0.00 AC: 0 AN: 15722

South Asian (SAS) AF: 0.000157 AC: 8 AN: 50840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2884

European-Non Finnish (NFE) AF: 0.0000221 AC: 18 AN: 815376

Other (OTH) AF: 0.0000491 AC: 2 AN: 40736

GnomAD4 genome AF: 0.0000238 AC: 2 AN: 84158 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 40894

African (AFR) AF: 0.0000602 AC: 1 AN: 16600

American (AMR) AF: 0.000139 AC: 1 AN: 7176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2256

East Asian (EAS) AF: 0.00 AC: 0 AN: 1882

South Asian (SAS) AF: 0.00 AC: 0 AN: 2580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 208

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 45054

Other (OTH) AF: 0.00 AC: 0 AN: 1168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=89/11	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;