chr5-102981413-G-A

Position:

• chr5-102981413-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001177306.2(PAM):​c.1483+6977G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,142 control chromosomes in the GnomAD database, including 5,630 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 0.26 (5630 hom., cov: 32)
• Consequence: PAM NM_001177306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.900

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAM	NM_001177306.2	c.1483+6977G>A		intron_variant		ENST00000438793.8	NP_001170777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAM	ENST00000438793.8	c.1483+6977G>A		intron_variant		1	NM_001177306.2	ENSP00000396493	P4

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39021 AN: 152024 Hom.: 5633 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.257 AC: 39035 AN: 152142 Hom.: 5630 Cov.: 32 AF XY: 0.256 AC XY: 19034 AN XY: 74370

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.256

Alfa AF: 0.291 Hom.: 2059

Bravo AF: 0.245

Asia WGS AF: 0.267 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.11

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

Publications

LitVar

Other links and lift over

dbSNP: rs10515341; hg19: chr5-102317117;