rs17296280

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0440

Publications

6 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PAMNM_001177306.2 linkc.2486-88A>C intron_variant Intron 23 of 25 ENST00000438793.8 NP_001170777.1 P19021-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PAMENST00000438793.8 linkc.2486-88A>C intron_variant Intron 23 of 25 1 NM_001177306.2 ENSP00000396493.3 P19021-1

Frequencies

GnomAD3 genomes
AF:
0.274
AC:
41635
AN:
151722
Hom.:
6177
Cov.:
31
show subpopulations
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
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
7529
15058
22587
30116
37645
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
2576
5152
7728
10304
12880
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.274
AC:
41646
AN:
151840
Hom.:
6175
Cov.:
31
AF XY:
0.271
AC XY:
20104
AN XY:
74196
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1460
2920
4381
5841
7301
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
422
844
1266
1688
2110
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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 v4.3

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

Publications

Other links and lift over

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