chr19-35511468-ACCACTGCTGCCG-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 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

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 Likely_benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMKN	NM_033317.5	c.849_860delCGGCAGCAGTGG	p.Gly284_Gly287del	disruptive_inframe_deletion	Exon 5 of 16	ENST00000339686.8	NP_201574.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMKN	ENST00000339686.8	c.849_860delCGGCAGCAGTGG	p.Gly284_Gly287del	disruptive_inframe_deletion	Exon 5 of 16	1	NM_033317.5	ENSP00000342012.3

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

Gnomad4 AFR exome AF: 0.0285

Gnomad4 AMR exome AF: 0.00805

Gnomad4 ASJ exome AF: 0.00458

Gnomad4 EAS exome AF: 0.0385

Gnomad4 SAS exome AF: 0.00144

Gnomad4 FIN exome AF: 0.00430

Gnomad4 NFE exome AF: 0.00155

Gnomad4 OTH exome AF: 0.00432

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

Gnomad4 AFR AF: 0.0359

Gnomad4 AMR AF: 0.00725

Gnomad4 ASJ AF: 0.00532

Gnomad4 EAS AF: 0.0293

Gnomad4 SAS AF: 0.00156

Gnomad4 FIN AF: 0.000763

Gnomad4 NFE AF: 0.00149

Gnomad4 OTH AF: 0.0101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs760401945; hg19: chr19-36002370;