20-1982979-C-T

Variant names:

• chr20-1982979-C-T
• rs149056587
• NM_024411.5:c.106G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024411.5(PDYN):​c.106G>A​(p.Gly36Ser) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G36C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDYN NM_024411.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09891945).

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.106G>A	p.Gly36Ser	missense	Exon 3 of 4	NP_077722.1	P01213
	PDYN	NM_001190892.1		c.106G>A	p.Gly36Ser	missense	Exon 2 of 3	NP_001177821.1	P01213
	PDYN	NM_001190898.3		c.106G>A	p.Gly36Ser	missense	Exon 3 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.106G>A	p.Gly36Ser	missense	Exon 3 of 4	ENSP00000217305.2	P01213
	PDYN	ENST00000539905.5	TSL:4	c.106G>A	p.Gly36Ser	missense	Exon 2 of 3	ENSP00000440185.1	P01213
	PDYN	ENST00000540134.5	TSL:4	c.106G>A	p.Gly36Ser	missense	Exon 3 of 4	ENSP00000442259.1	P01213

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.66
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.37
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.99	N
REVEL	Benign	0.14
Sift	Benign	0.65	T
Sift4G	Benign	0.80	T
Polyphen		0.029	B
Vest4		0.29
MutPred		0.48		Gain of disorder (P = 0.0216)
MVP		0.55
MPC		0.048
ClinPred		0.96	D
GERP RS		0.43
Varity_R		0.034
gMVP		0.37
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs149056587; hg19: chr20-1963625;