5-102828414-T-C

Variant names:

• chr5-102828414-T-C
• rs469326
• NM_001177306.2:c.-373-37409T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001177306.2(PAM):​c.-373-37409T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 151,822 control chromosomes in the GnomAD database, including 35,913 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 0.68 (35913 hom., cov: 30)
• Consequence: PAM NM_001177306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAM	NM_001177306.2	c.-373-37409T>C		intron_variant	Intron 1 of 25	ENST00000438793.8	NP_001170777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAM	ENST00000438793.8	c.-373-37409T>C		intron_variant	Intron 1 of 25	1	NM_001177306.2	ENSP00000396493.3

Frequencies

GnomAD3 genomes AF: 0.685 AC: 103916 AN: 151704 Hom.: 35882 Cov.: 30

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.718

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.685 AC: 103997 AN: 151822 Hom.: 35913 Cov.: 30 AF XY: 0.689 AC XY: 51084 AN XY: 74196

African (AFR) AF: 0.734 AC: 30355 AN: 41372

American (AMR) AF: 0.714 AC: 10886 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 2794 AN: 3470

East Asian (EAS) AF: 0.737 AC: 3805 AN: 5160

South Asian (SAS) AF: 0.808 AC: 3886 AN: 4810

European-Finnish (FIN) AF: 0.624 AC: 6554 AN: 10502

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43436 AN: 67942

Other (OTH) AF: 0.722 AC: 1521 AN: 2106

Alfa AF: 0.641 Hom.: 4334

Bravo AF: 0.693

Asia WGS AF: 0.780 AC: 2715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.0
DANN	Benign	0.52
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs469326; hg19: chr5-102164118;