NM_024411.5:c.600T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024411.5(PDYN):c.600T>C(p.His200His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,502 control chromosomes in the GnomAD database, including 13,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2318 hom., cov: 31)

Exomes 𝑓: 0.12 ( 11033 hom. )

Consequence

PDYN
NM_024411.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.93

Publications

22 publications found

Variant links:

Genes affected

PDYN (HGNC:8820): (prodynorphin) The protein encoded by this gene is a preproprotein that is proteolytically processed to form the secreted opioid peptides beta-neoendorphin, dynorphin, leu-enkephalin, rimorphin, and leumorphin. These peptides are ligands for the kappa-type of opioid receptor. Dynorphin is involved in modulating responses to several psychoactive substances, including cocaine. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2010]

PDYN links:

PDYN-AS1 (HGNC:53462): (PDYN antisense RNA 1)

PDYN-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 20-1980488-A-G is Benign according to our data. Variant chr20-1980488-A-G is described in ClinVar as Benign. ClinVar VariationId is 337834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.93 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDYN	NM_024411.5 link	c.600T>C	p.His200His	synonymous_variant	Exon 4 of 4	ENST00000217305.3	NP_077722.1	P01213

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDYN	ENST00000217305.3 link	c.600T>C	p.His200His	synonymous_variant	Exon 4 of 4	1	NM_024411.5	ENSP00000217305.2		P01213

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23448

AN:

151562

Hom.:

2312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.0901

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.0627

Gnomad FIN

AF:

0.0799

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.175

GnomAD2 exomes

AF:

0.106

AC:

26563

AN:

251350

AF XY:

0.103

show subpopulations

Gnomad AFR exome

AF:

0.285

Gnomad AMR exome

AF:

0.0784

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0795

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.122

GnomAD4 exome

AF:

0.115

AC:

168373

AN:

1461820

Hom.:

11033

Cov.:

AF XY:

0.114

AC XY:

82707

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.291

AC:

9749

AN:

33476

American (AMR)

AF:

0.0832

AC:

3719

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

3039

AN:

26136

East Asian (EAS)

AF:

0.000202

AC:

AN:

39700

South Asian (SAS)

AF:

0.0693

AC:

5978

AN:

86252

European-Finnish (FIN)

AF:

0.0814

AC:

4351

AN:

53420

Middle Eastern (MID)

AF:

0.188

AC:

1085

AN:

5768

European-Non Finnish (NFE)

AF:

0.120

AC:

133207

AN:

1111950

Other (OTH)

AF:

0.120

AC:

7237

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

9320

18640

27961

37281

46601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4850

9700

14550

19400

24250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.155

AC:

23480

AN:

151682

Hom.:

2318

Cov.:

AF XY:

0.151

AC XY:

11159

AN XY:

74098

show subpopulations

African (AFR)

AF:

0.279

AC:

11523

AN:

41308

American (AMR)

AF:

0.122

AC:

1864

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

417

AN:

3468

East Asian (EAS)

AF:

0.00156

AC:

AN:

5136

South Asian (SAS)

AF:

0.0638

AC:

306

AN:

4796

European-Finnish (FIN)

AF:

0.0799

AC:

842

AN:

10540

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.118

AC:

8003

AN:

67874

Other (OTH)

AF:

0.174

AC:

367

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

940

1881

2821

3762

4702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.131

Hom.:

2810

Bravo

AF:

0.165

Asia WGS

AF:

0.0500

AC:

175

AN:

3478

EpiCase

AF:

0.124

EpiControl

AF:

0.129

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spinocerebellar ataxia type 23

Benign:4

Oct 10, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Sep 20, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.012

(source)

DANN

Benign

0.36

PhyloP100

-2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over