chr8-28339078-C-T

Variant names:

• chr8-28339078-C-T
• rs866352421
• NM_006228.5:c.165C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_006228.5(PNOC):​c.165C>T​(p.Ser55Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,260 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PNOC NM_006228.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 0 publications found

Genes affected

PNOC (HGNC:9163): (prepronociceptin) This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include nociceptin, nocistatin, and orphanin FQ2 (OFQ2). Nociceptin, also known as orphanin FQ, is a 17-amino acid neuropeptide that binds to the nociceptin receptor to induce increased pain sensitivity, and may additionally regulate body temperature, learning and memory, and hunger. Another product of the encoded preproprotein, nocistatin, may inhibit the effects of nociceptin. [provided by RefSeq, Jul 2015]

ENSG00000253690 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=-0.12 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006228.5. 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
	PNOC	NM_006228.5	MANE Select	c.165C>T	p.Ser55Ser	synonymous	Exon 3 of 4	NP_006219.1	Q13519-1
	PNOC	NM_001284244.2		c.-28C>T		5_prime_UTR	Exon 2 of 3	NP_001271173.1	Q13519-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNOC	ENST00000301908.8	TSL:1 MANE Select	c.165C>T	p.Ser55Ser	synonymous	Exon 3 of 4	ENSP00000301908.3	Q13519-1
	PNOC	ENST00000923262.1		c.165C>T	p.Ser55Ser	synonymous	Exon 3 of 3	ENSP00000593321.1
	PNOC	ENST00000518479.5	TSL:4	c.165C>T	p.Ser55Ser	synonymous	Exon 3 of 3	ENSP00000428059.1	E7EVP0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1441260 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 711930

African (AFR) AF: 0.00 AC: 0 AN: 33086

American (AMR) AF: 0.00 AC: 0 AN: 44220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25920

East Asian (EAS) AF: 0.00 AC: 0 AN: 39014

South Asian (SAS) AF: 0.00 AC: 0 AN: 85798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53242

Middle Eastern (MID) AF: 0.000350 AC: 2 AN: 5708

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094908

Other (OTH) AF: 0.00 AC: 0 AN: 59364

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
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		-0.12
PromoterAI		-0.017	Neutral

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: rs866352421; hg19: chr8-28196595;