NM_024411.5:c.*771T>C

Variant names:

• chr20-1979552-A-G
• rs910079
• NM_024411.5:c.*771T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024411.5(PDYN):​c.*771T>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 0.371 in 152,130 control chromosomes in the GnomAD database, including 11,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11844 hom., cov: 32)
  • Exomes 𝑓: 0.27 (3 hom.)
• Consequence: PDYN NM_024411.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.506
• Publications: 17 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 20-1979552-A-G is Benign according to our data. Variant chr20-1979552-A-G is described in ClinVar as Benign. ClinVar VariationId is 337819.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDYN	NM_024411.5	MANE Select	c.*771T>C		3_prime_UTR	Exon 4 of 4	NP_077722.1	P01213
	PDYN	NM_001190892.1		c.*771T>C		3_prime_UTR	Exon 3 of 3	NP_001177821.1	P01213
	PDYN	NM_001190898.3		c.*771T>C		3_prime_UTR	Exon 4 of 4	NP_001177827.1	P01213

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDYN	ENST00000217305.3	TSL:1 MANE Select	c.*771T>C		3_prime_UTR	Exon 4 of 4	ENSP00000217305.2	P01213
	PDYN	ENST00000539905.5	TSL:4	c.*771T>C		3_prime_UTR	Exon 3 of 3	ENSP00000440185.1	P01213
	PDYN	ENST00000540134.5	TSL:4	c.*771T>C		3_prime_UTR	Exon 4 of 4	ENSP00000442259.1	P01213

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56272 AN: 151922 Hom.: 11809 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.267 AC: 24 AN: 90 Hom.: 3 Cov.: 0 AF XY: 0.250 AC XY: 10 AN XY: 40

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.375 AC: 3 AN: 8

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.256 AC: 21 AN: 82

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.371 AC: 56373 AN: 152040 Hom.: 11844 Cov.: 32 AF XY: 0.377 AC XY: 28038 AN XY: 74322

African (AFR) AF: 0.497 AC: 20612 AN: 41432

American (AMR) AF: 0.342 AC: 5222 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3470

East Asian (EAS) AF: 0.846 AC: 4372 AN: 5168

South Asian (SAS) AF: 0.526 AC: 2535 AN: 4822

European-Finnish (FIN) AF: 0.302 AC: 3193 AN: 10576

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18334 AN: 67984

Other (OTH) AF: 0.360 AC: 761 AN: 2112

Alfa AF: 0.305 Hom.: 9811

Bravo AF: 0.380

Asia WGS AF: 0.686 AC: 2383 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Spinocerebellar ataxia type 23 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.56
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs910079; hg19: chr20-1960198;