rs17296280

Variant names:

• chr5-103025043-A-C
• rs17296280
• NM_001177306.2:c.2486-88A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-103025043-A-C
• chr5-103025043-A-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.2486-88A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 843,236 control chromosomes in the GnomAD database, including 39,938 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 0.27 (6175 hom., cov: 31)
  • Exomes 𝑓: 0.31 (33763 hom.)
• Consequence: PAM NM_001177306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177306.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAM	NM_001177306.2	MANE Select	c.2486-88A>C		intron	N/A	NP_001170777.1
	PAM	NM_001319943.1		c.2540-88A>C		intron	N/A	NP_001306872.1
	PAM	NM_000919.4		c.2486-88A>C		intron	N/A	NP_000910.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAM	ENST00000438793.8	TSL:1 MANE Select	c.2486-88A>C		intron	N/A	ENSP00000396493.3
	PAM	ENST00000304400.12	TSL:1	c.2486-91A>C		intron	N/A	ENSP00000306100.8
	PAM	ENST00000455264.7	TSL:1	c.2486-3142A>C		intron	N/A	ENSP00000403461.2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41635 AN: 151722 Hom.: 6177 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.305 AC: 210930 AN: 691396 Hom.: 33763 AF XY: 0.300 AC XY: 109186 AN XY: 364556

African (AFR) AF: 0.170 AC: 3050 AN: 17992

American (AMR) AF: 0.228 AC: 7378 AN: 32388

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 4565 AN: 16898

East Asian (EAS) AF: 0.377 AC: 13580 AN: 36014

South Asian (SAS) AF: 0.162 AC: 9378 AN: 57894

European-Finnish (FIN) AF: 0.334 AC: 12999 AN: 38956

Middle Eastern (MID) AF: 0.198 AC: 579 AN: 2928

European-Non Finnish (NFE) AF: 0.329 AC: 149161 AN: 453518

Other (OTH) AF: 0.294 AC: 10240 AN: 34808

GnomAD4 genome AF: 0.274 AC: 41646 AN: 151840 Hom.: 6175 Cov.: 31 AF XY: 0.271 AC XY: 20104 AN XY: 74196

African (AFR) AF: 0.169 AC: 6997 AN: 41452

American (AMR) AF: 0.262 AC: 3986 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3466

East Asian (EAS) AF: 0.365 AC: 1882 AN: 5160

South Asian (SAS) AF: 0.161 AC: 773 AN: 4804

European-Finnish (FIN) AF: 0.333 AC: 3503 AN: 10512

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.331 AC: 22487 AN: 67906

Other (OTH) AF: 0.282 AC: 594 AN: 2110

Alfa AF: 0.173 Hom.: 383

Bravo AF: 0.264

Asia WGS AF: 0.248 AC: 864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.6
DANN	Benign	0.69
PhyloP100		0.044
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17296280; hg19: chr5-102360747; COSMIC: COSV57211114;