Genetic Variant PDYN:c.*743T>C (chr20-1979580-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024411.5(PDYN):c.*743T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,474 control chromosomes in the GnomAD database, including 11,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11174 hom., cov: 32)

Exomes 𝑓: 0.18 ( 7 hom. )

Consequence

PDYN
NM_024411.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.264

Publications

32 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 20-1979580-A-G is Benign according to our data. Variant chr20-1979580-A-G is described in ClinVar as Benign. ClinVar VariationId is 337820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024411.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDYN	NM_024411.5	MANE Select	c.*743T>C	3_prime_UTR	Exon 4 of 4	NP_077722.1	P01213
PDYN	NM_001190892.1		c.*743T>C	3_prime_UTR	Exon 3 of 3	NP_001177821.1	P01213
PDYN	NM_001190898.3		c.*743T>C	3_prime_UTR	Exon 4 of 4	NP_001177827.1	P01213

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDYN	ENST00000217305.3	TSL:1 MANE Select	c.*743T>C	3_prime_UTR	Exon 4 of 4	ENSP00000217305.2	P01213
PDYN	ENST00000539905.5	TSL:4	c.*743T>C	3_prime_UTR	Exon 3 of 3	ENSP00000440185.1	P01213
PDYN	ENST00000540134.5	TSL:4	c.*743T>C	3_prime_UTR	Exon 4 of 4	ENSP00000442259.1	P01213

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54546

AN:

151978

Hom.:

11144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.477

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.847

Gnomad SAS

AF:

0.524

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.344

GnomAD4 exome

AF:

0.184

AC:

AN:

376

Hom.:

Cov.:

AF XY:

0.176

AC XY:

AN XY:

204

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.310

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.169

AC:

AN:

314

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.359

AC:

54643

AN:

152098

Hom.:

11174

Cov.:

AF XY:

0.365

AC XY:

27159

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.478

AC:

19812

AN:

41480

American (AMR)

AF:

0.336

AC:

5132

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

956

AN:

3470

East Asian (EAS)

AF:

0.846

AC:

4368

AN:

5166

South Asian (SAS)

AF:

0.524

AC:

2529

AN:

4826

European-Finnish (FIN)

AF:

0.283

AC:

2988

AN:

10574

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.262

AC:

17825

AN:

67982

Other (OTH)

AF:

0.351

AC:

742

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1668

3336

5004

6672

8340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.321

Hom.:

3662

Bravo

AF:

0.369

Asia WGS

AF:

0.684

AC:

2378

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Spinocerebellar ataxia type 23 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.6

(source)

DANN

Benign

0.63

PhyloP100

0.26

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over