Genetic Variant PENK:c.-3-167C>A (chr8-56446123-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001135690.3(PENK):c.-3-167C>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PENK
NM_001135690.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.223

Publications

6 publications found

Variant links:

Genes affected

PENK (HGNC:8831): (proenkephalin) This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include the pentapeptide opioids Met-enkephalin and Leu-enkephalin, which are stored in synaptic vesicles, then released into the synapse where they bind to mu- and delta-opioid receptors to modulate the perception of pain. Other non-opioid cleavage products may function in distinct biological activities. [provided by RefSeq, Jul 2015]

PENK links:

PENK-AS1 (HGNC:55519): (PENK antisense RNA 1)

PENK-AS1 links:

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ACMG classification

Classification was made for transcript

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 (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PENK	NM_001135690.3 link	c.-3-167C>A		intron_variant	Intron 2 of 3	ENST00000451791.7	NP_001129162.1	P01210A0A024R7V4
PENK-AS1	NR_125813.1 link	n.317G>T		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PENK	ENST00000451791.7 link	c.-3-167C>A		intron_variant	Intron 2 of 3	1	NM_001135690.3	ENSP00000400894.2		P01210

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

580880

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

296514

African (AFR)

AF:

0.00

AC:

AN:

14250

American (AMR)

AF:

0.00

AC:

AN:

18342

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14054

East Asian (EAS)

AF:

0.00

AC:

AN:

30974

South Asian (SAS)

AF:

0.00

AC:

AN:

43694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2178

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

389992

Other (OTH)

AF:

0.00

AC:

AN:

29832

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.7

(source)

DANN

Benign

0.24

PhyloP100

-0.22

PromoterAI

-0.011

Neutral

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over