rs5855

Positions:

• chr5-103029482-G-A
• chr5-103029482-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001177306.2(PAM):​c.*417G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.689 in 155,140 control chromosomes in the GnomAD database, including 37,036 homozygotes. 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: 𝑓 0.69 (36265 hom., cov: 32)
  • Exomes 𝑓: 0.70 (771 hom.)
• Consequence: PAM NM_001177306.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.43

Genes affected

PAM (HGNC:8596): (peptidylglycine alpha-amidating monooxygenase) This gene encodes a multifunctional protein. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme includes two domains with distinct catalytic activities, a peptidylglycine alpha-hydroxylating monooxygenase (PHM) domain and a peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) domain. These catalytic domains work sequentially to catalyze the conversion of neuroendocrine peptides to active alpha-amidated products. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

PAM (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAM	NM_001177306.2	c.*417G>A		3_prime_UTR_variant	26/26	ENST00000438793.8	NP_001170777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAM	ENST00000438793.8	c.*417G>A		3_prime_UTR_variant	26/26	1	NM_001177306.2	ENSP00000396493.3

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104708 AN: 151962 Hom.: 36249 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.707

GnomAD4 exome AF: 0.704 AC: 2155 AN: 3060 Hom.: 771 Cov.: 0 AF XY: 0.700 AC XY: 1141 AN XY: 1630

Gnomad4 AFR exome AF: 0.767

Gnomad4 AMR exome AF: 0.758

Gnomad4 ASJ exome AF: 0.674

Gnomad4 EAS exome AF: 0.579

Gnomad4 SAS exome AF: 0.813

Gnomad4 FIN exome AF: 0.687

Gnomad4 NFE exome AF: 0.709

Gnomad4 OTH exome AF: 0.688

GnomAD4 genome AF: 0.689 AC: 104780 AN: 152080 Hom.: 36265 Cov.: 32 AF XY: 0.692 AC XY: 51417 AN XY: 74354

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.709

Alfa AF: 0.690 Hom.: 40542

Bravo AF: 0.691

Asia WGS AF: 0.722 AC: 2513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	16
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5855; hg19: chr5-102365186;