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5-102960019-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001177306.2(PAM):c.1050C>T(p.Pro350=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,610,326 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 8 hom., cov: 32)
Exomes 𝑓: 0.011 ( 110 hom. )

Consequence

PAM
NM_001177306.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.844
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-102960019-C-T is Benign according to our data. Variant chr5-102960019-C-T is described in ClinVar as [Benign]. Clinvar id is 777978.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.844 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PAMNM_001177306.2 linkuse as main transcriptc.1050C>T p.Pro350= synonymous_variant 13/26 ENST00000438793.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PAMENST00000438793.8 linkuse as main transcriptc.1050C>T p.Pro350= synonymous_variant 13/261 NM_001177306.2 P4P19021-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00667
AC:
1013
AN:
151886
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00210
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00243
Gnomad ASJ
AF:
0.00374
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00151
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0124
Gnomad OTH
AF:
0.00672
GnomAD3 exomes
AF:
0.00700
AC:
1754
AN:
250570
Hom.:
9
AF XY:
0.00686
AC XY:
929
AN XY:
135416
show subpopulations
Gnomad AFR exome
AF:
0.00209
Gnomad AMR exome
AF:
0.00319
Gnomad ASJ exome
AF:
0.00468
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000458
Gnomad FIN exome
AF:
0.00282
Gnomad NFE exome
AF:
0.0127
Gnomad OTH exome
AF:
0.00755
GnomAD4 exome
AF:
0.0114
AC:
16577
AN:
1458322
Hom.:
110
Cov.:
29
AF XY:
0.0109
AC XY:
7925
AN XY:
725628
show subpopulations
Gnomad4 AFR exome
AF:
0.00159
Gnomad4 AMR exome
AF:
0.00311
Gnomad4 ASJ exome
AF:
0.00452
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000464
Gnomad4 FIN exome
AF:
0.00343
Gnomad4 NFE exome
AF:
0.0140
Gnomad4 OTH exome
AF:
0.00851
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00666
AC:
1013
AN:
152004
Hom.:
8
Cov.:
32
AF XY:
0.00610
AC XY:
453
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.00210
Gnomad4 AMR
AF:
0.00243
Gnomad4 ASJ
AF:
0.00374
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000416
Gnomad4 FIN
AF:
0.00151
Gnomad4 NFE
AF:
0.0124
Gnomad4 OTH
AF:
0.00665
Alfa
AF:
0.0102
Hom.:
4
Bravo
AF:
0.00680
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.0111
EpiControl
AF:
0.0121

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.31
Cadd
Benign
8.8
Dann
Benign
0.52

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2217252; hg19: chr5-102295723; COSMIC: COSV57213532; API