NM_024411.5:c.*656T>C

Variant names:

• chr20-1979667-A-G
• rs10485703
• NM_024411.5:c.*656T>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.*656T>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 0.117 in 157,242 control chromosomes in the GnomAD database, including 1,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1176 hom., cov: 31)
  • Exomes 𝑓: 0.081 (20 hom.)
• Consequence: PDYN NM_024411.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.664
• Publications: 12 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=-0.82).
• BP6: Variant 20-1979667-A-G is Benign according to our data. Variant chr20-1979667-A-G is described in ClinVar as Benign. ClinVar VariationId is 337822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 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.*656T>C		3_prime_UTR	Exon 4 of 4	NP_077722.1	P01213
	PDYN	NM_001190892.1		c.*656T>C		3_prime_UTR	Exon 3 of 3	NP_001177821.1	P01213
	PDYN	NM_001190898.3		c.*656T>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.*656T>C		3_prime_UTR	Exon 4 of 4	ENSP00000217305.2	P01213
	PDYN	ENST00000539905.5	TSL:4	c.*656T>C		3_prime_UTR	Exon 3 of 3	ENSP00000440185.1	P01213
	PDYN	ENST00000540134.5	TSL:4	c.*656T>C		3_prime_UTR	Exon 4 of 4	ENSP00000442259.1	P01213

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18036 AN: 152032 Hom.: 1174 Cov.: 31

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0598

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.0805 AC: 410 AN: 5092 Hom.: 20 Cov.: 0 AF XY: 0.0805 AC XY: 216 AN XY: 2684

African (AFR) AF: 0.188 AC: 3 AN: 16

American (AMR) AF: 0.0619 AC: 87 AN: 1406

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 3 AN: 14

East Asian (EAS) AF: 0.00 AC: 0 AN: 80

South Asian (SAS) AF: 0.0389 AC: 23 AN: 592

European-Finnish (FIN) AF: 0.143 AC: 2 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0989 AC: 278 AN: 2810

Other (OTH) AF: 0.0875 AC: 14 AN: 160

GnomAD4 genome AF: 0.119 AC: 18057 AN: 152150 Hom.: 1176 Cov.: 31 AF XY: 0.115 AC XY: 8582 AN XY: 74398

African (AFR) AF: 0.168 AC: 6955 AN: 41476

American (AMR) AF: 0.0998 AC: 1526 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 371 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5172

South Asian (SAS) AF: 0.0609 AC: 294 AN: 4826

European-Finnish (FIN) AF: 0.0813 AC: 863 AN: 10612

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7619 AN: 67988

Other (OTH) AF: 0.138 AC: 291 AN: 2114

Alfa AF: 0.120 Hom.: 1123

Bravo AF: 0.124

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

ClinVar submissions

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	-0.82
CADD	Benign	4.2
DANN	Benign	0.84
PhyloP100		0.66
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: rs10485703; hg19: chr20-1960313;