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17-43953334-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001394028.1(PYY):c.150C>T(p.Ala50=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,612,964 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0022 ( 12 hom. )

Consequence

PYY
NM_001394028.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.748
Variant links:
Genes affected
PYY (HGNC:9748): (peptide YY) This gene encodes a member of the neuropeptide Y (NPY) family of peptides. The encoded preproprotein is proteolytically processed to generate two alternative peptide products that differ in length by three amino acids. These peptides, secreted by endocrine cells in the gut, exhibit different binding affinities for each of the neuropeptide Y receptors. Binding of the encoded peptides to these receptors mediates regulation of pancreatic secretion, gut mobility and energy homeostasis. Rare variations in this gene could increase susceptibility to obesity and elevated serum levels of the encoded peptides may be associated with anorexia nervosa. [provided by RefSeq, Feb 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-43953334-G-A is Benign according to our data. Variant chr17-43953334-G-A is described in ClinVar as [Benign]. Clinvar id is 709316.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=-0.748 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00215 (3144/1460670) while in subpopulation MID AF= 0.0187 (108/5762). AF 95% confidence interval is 0.0159. There are 12 homozygotes in gnomad4_exome. There are 1567 alleles in male gnomad4_exome subpopulation. Median coverage is 49. This position pass quality control queck.
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 GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PYYNM_001394028.1 linkuse as main transcriptc.150C>T p.Ala50= synonymous_variant 2/4 ENST00000692052.1
PYYNM_004160.6 linkuse as main transcriptc.150C>T p.Ala50= synonymous_variant 5/7
PYYNM_001394029.1 linkuse as main transcriptc.150C>T p.Ala50= synonymous_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PYYENST00000692052.1 linkuse as main transcriptc.150C>T p.Ala50= synonymous_variant 2/4 NM_001394028.1 P1P10082-1
PYYENST00000360085.6 linkuse as main transcriptc.150C>T p.Ala50= synonymous_variant 5/71 P1P10082-1
PYYENST00000592796.2 linkuse as main transcriptc.150C>T p.Ala50= synonymous_variant 2/31 P10082-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00212
AC:
322
AN:
152176
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000627
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00399
Gnomad ASJ
AF:
0.0133
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00207
Gnomad FIN
AF:
0.00188
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.00215
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00238
AC:
586
AN:
246402
Hom.:
2
AF XY:
0.00236
AC XY:
316
AN XY:
134012
show subpopulations
Gnomad AFR exome
AF:
0.000957
Gnomad AMR exome
AF:
0.00170
Gnomad ASJ exome
AF:
0.0131
Gnomad EAS exome
AF:
0.0000549
Gnomad SAS exome
AF:
0.00122
Gnomad FIN exome
AF:
0.00252
Gnomad NFE exome
AF:
0.00239
Gnomad OTH exome
AF:
0.00451
GnomAD4 exome
AF:
0.00215
AC:
3144
AN:
1460670
Hom.:
12
Cov.:
49
AF XY:
0.00216
AC XY:
1567
AN XY:
726664
show subpopulations
Gnomad4 AFR exome
AF:
0.00287
Gnomad4 AMR exome
AF:
0.00215
Gnomad4 ASJ exome
AF:
0.0148
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00107
Gnomad4 FIN exome
AF:
0.00217
Gnomad4 NFE exome
AF:
0.00182
Gnomad4 OTH exome
AF:
0.00380
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00211
AC:
322
AN:
152294
Hom.:
0
Cov.:
33
AF XY:
0.00203
AC XY:
151
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.000673
Gnomad4 AMR
AF:
0.00398
Gnomad4 ASJ
AF:
0.0133
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00207
Gnomad4 FIN
AF:
0.00188
Gnomad4 NFE
AF:
0.00215
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00276
Hom.:
0
Bravo
AF:
0.00243
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.00322
EpiControl
AF:
0.00321

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 testingInvitaeJul 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
10
Dann
Benign
0.96

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: rs138375613; hg19: chr17-42030702; API