5-102831450-C-T

Variant names:

• chr5-102831450-C-T
• rs467693
• NM_001177306.2:c.-373-34373C>T

Variant summary

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

The NM_001177306.2(PAM):​c.-373-34373C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 148,746 control chromosomes in the GnomAD database, including 24,237 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 0.57 (24237 hom., cov: 29)
• Consequence: PAM NM_001177306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAM	NM_001177306.2	c.-373-34373C>T		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.-373-34373C>T		intron_variant	Intron 1 of 25	1	NM_001177306.2	ENSP00000396493.3

Frequencies

GnomAD3 genomes AF: 0.566 AC: 84059 AN: 148638 Hom.: 24232 Cov.: 29

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.565 AC: 84081 AN: 148746 Hom.: 24237 Cov.: 29 AF XY: 0.570 AC XY: 41390 AN XY: 72584

African (AFR) AF: 0.415 AC: 16508 AN: 39786

American (AMR) AF: 0.658 AC: 9909 AN: 15054

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2445 AN: 3454

East Asian (EAS) AF: 0.597 AC: 3027 AN: 5072

South Asian (SAS) AF: 0.660 AC: 3115 AN: 4722

European-Finnish (FIN) AF: 0.609 AC: 6123 AN: 10046

Middle Eastern (MID) AF: 0.661 AC: 193 AN: 292

European-Non Finnish (NFE) AF: 0.609 AC: 40997 AN: 67354

Other (OTH) AF: 0.606 AC: 1253 AN: 2066

Alfa AF: 0.605 Hom.: 41629

Bravo AF: 0.556

Asia WGS AF: 0.624 AC: 2147 AN: 3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.48
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs467693; hg19: chr5-102167154;