Variant 19-35511479-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_033317.5(DMKN):c.850G>A(p.Gly284Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 955,198 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0088 ( 5 hom., cov: 27)

Exomes 𝑓: 0.0016 ( 18 hom. )

Consequence

DMKN
NM_033317.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.40

Variant links:

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]

DMKN links:

DMKN (HGNC:):

DMKN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.958446E-4).

BP6

Variant 19-35511479-C-T is Benign according to our data. Variant chr19-35511479-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2357089.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00875 (909/103846) while in subpopulation AFR AF= 0.0296 (843/28446). AF 95% confidence interval is 0.028. There are 5 homozygotes in gnomad4. There are 424 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMKN	NM_033317.5 linkuse as main transcript	c.850G>A	p.Gly284Ser	missense_variant	5/16	ENST00000339686.8	NP_201574.4	Q6E0U4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMKN	ENST00000339686.8 linkuse as main transcript	c.850G>A	p.Gly284Ser	missense_variant	5/16	1	NM_033317.5	ENSP00000342012.3		Q6E0U4-1

Frequencies

GnomAD3 genomes

AF:

0.00871

AC:

904

AN:

103776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0295

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00453

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00275

Gnomad SAS

AF:

0.00172

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00472

Gnomad NFE

AF:

0.000140

Gnomad OTH

AF:

0.00656

GnomAD4 exome

AF:

0.00159

AC:

1352

AN:

851352

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

657

AN XY:

424824

show subpopulations

Gnomad4 AFR exome

AF:

0.0347

Gnomad4 AMR exome

AF:

0.00308

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00600

Gnomad4 SAS exome

AF:

0.00117

Gnomad4 FIN exome

AF:

0.000561

Gnomad4 NFE exome

AF:

0.000382

Gnomad4 OTH exome

AF:

0.00353

GnomAD4 genome

AF:

0.00875

AC:

909

AN:

103846

Hom.:

Cov.:

AF XY:

0.00844

AC XY:

424

AN XY:

50238

show subpopulations

Gnomad4 AFR

AF:

0.0296

Gnomad4 AMR

AF:

0.00453

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00275

Gnomad4 SAS

AF:

0.00138

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000140

Gnomad4 OTH

AF:

0.00648

Alfa

AF:

0.116

Hom.:

142

ExAC

AF:

0.0309

AC:

2191

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.20

DANN

Benign

0.36

DEOGEN2

Benign

0.0024

T;.;.;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00055

LIST_S2

Benign

0.33

T;T;T;T;T

MetaRNN

Benign

0.0010

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.61

N;N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.70

N;N;N;N;N

REVEL

Benign

0.026

Sift

Pathogenic

0.0

D;D;T;D;D

Sift4G

Benign

0.37

T;T;T;T;T

Polyphen

0.012

B;.;B;B;B

Vest4

0.20

MPC

0.067

ClinPred

0.19

GERP RS

-3.4

Varity_R

0.074

gMVP

0.30

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over