NM_024411.5:c.217A>G

Variant names:

• chr20-1980871-T-C
• rs786205212
• NM_024411.5:c.217A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024411.5(PDYN):​c.217A>G​(p.Thr73Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDYN NM_024411.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.165
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06074822).

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.217A>G	p.Thr73Ala	missense	Exon 4 of 4	NP_077722.1	P01213
	PDYN	NM_001190892.1		c.217A>G	p.Thr73Ala	missense	Exon 3 of 3	NP_001177821.1	P01213
	PDYN	NM_001190898.3		c.217A>G	p.Thr73Ala	missense	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.217A>G	p.Thr73Ala	missense	Exon 4 of 4	ENSP00000217305.2	P01213
	PDYN	ENST00000539905.5	TSL:4	c.217A>G	p.Thr73Ala	missense	Exon 3 of 3	ENSP00000440185.1	P01213
	PDYN	ENST00000540134.5	TSL:4	c.217A>G	p.Thr73Ala	missense	Exon 4 of 4	ENSP00000442259.1	P01213

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Spinocerebellar ataxia type 23 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.22
DANN	Benign	0.74
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.43	N
PhyloP100		-0.17
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.056
Sift	Benign	0.47	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.022
MutPred		0.25		Loss of phosphorylation at T73 (P = 0.0311)
MVP		0.57
MPC		0.027
ClinPred		0.055	T
GERP RS		-2.1
Varity_R		0.025
gMVP		0.18
Mutation Taster		=95/5	polymorphism

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: rs786205212; hg19: chr20-1961517; COSMIC: COSV99453357;