5-102856011-C-T

Variant names:

• chr5-102856011-C-T
• rs32680
• NM_001177306.2:c.-373-9812C>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.-373-9812C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 151,962 control chromosomes in the GnomAD database, including 3,207 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 0.18 (3207 hom., cov: 32)
• Consequence: PAM NM_001177306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653
• Publications: 11 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAM	NM_001177306.2	c.-373-9812C>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.-373-9812C>T		intron_variant	Intron 1 of 25	1	NM_001177306.2	ENSP00000396493.3

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27371 AN: 151844 Hom.: 3206 Cov.: 32

Gnomad AFR AF: 0.0443

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.0838

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.180 AC: 27370 AN: 151962 Hom.: 3207 Cov.: 32 AF XY: 0.178 AC XY: 13254 AN XY: 74272

African (AFR) AF: 0.0441 AC: 1830 AN: 41458

American (AMR) AF: 0.177 AC: 2696 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3468

East Asian (EAS) AF: 0.158 AC: 812 AN: 5152

South Asian (SAS) AF: 0.0839 AC: 404 AN: 4818

European-Finnish (FIN) AF: 0.303 AC: 3197 AN: 10538

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17306 AN: 67948

Other (OTH) AF: 0.176 AC: 372 AN: 2108

Alfa AF: 0.194 Hom.: 3473

Bravo AF: 0.166

Asia WGS AF: 0.115 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.69
PhyloP100		-0.65

Splicing

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

Other links and lift over

dbSNP: rs32680; hg19: chr5-102191715;