Genetic Variant ENST00000360085.6:c.-114G>A (chr17-43953963-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000360085.6(PYY):c.-114G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 154,246 control chromosomes in the GnomAD database, including 28,981 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 0.61 ( 28523 hom., cov: 31)

Exomes 𝑓: 0.62 ( 458 hom. )

Consequence

PYY
ENST00000360085.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.307

Publications

16 publications found

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]

PYY links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PYY	NM_004160.6 link	c.-114G>A	5_prime_UTR_variant	Exon 4 of 7		NP_004151.4	P10082-1
PYY	NM_001394028.1 link	c.-114G>A	upstream_gene_variant		ENST00000692052.1	NP_001380957.1
PYY	NM_001394029.1 link	c.-114G>A	upstream_gene_variant			NP_001380958.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PYY	ENST00000360085.6 link	c.-114G>A	5_prime_UTR_variant	Exon 4 of 7	1		ENSP00000353198.1	P10082-1
PYY	ENST00000692052.1 link	c.-114G>A	upstream_gene_variant			NM_001394028.1	ENSP00000509262.1	P10082-1
PYY	ENST00000592796.2 link	c.-114G>A	upstream_gene_variant		1		ENSP00000467310.1	P10082-2

Frequencies

GnomAD3 genomes

AF:

0.605

AC:

91917

AN:

151836

Hom.:

28513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.496

Gnomad AMI

AF:

0.558

Gnomad AMR

AF:

0.601

Gnomad ASJ

AF:

0.643

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.729

Gnomad FIN

AF:

0.701

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.669

Gnomad OTH

AF:

0.593

GnomAD4 exome

AF:

0.619

AC:

1419

AN:

2292

Hom.:

458

Cov.:

AF XY:

0.624

AC XY:

741

AN XY:

1188

show subpopulations

African (AFR)

AF:

0.452

AC:

AN:

American (AMR)

AF:

0.750

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.625

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.694

AC:

AN:

European-Finnish (FIN)

AF:

0.693

AC:

294

AN:

424

Middle Eastern (MID)

AF:

0.586

AC:

652

AN:

1112

European-Non Finnish (NFE)

AF:

0.668

AC:

286

AN:

428

Other (OTH)

AF:

0.586

AC:

AN:

152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.605

AC:

91945

AN:

151954

Hom.:

28523

Cov.:

AF XY:

0.608

AC XY:

45179

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.495

AC:

20539

AN:

41454

American (AMR)

AF:

0.600

AC:

9149

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.643

AC:

2228

AN:

3464

East Asian (EAS)

AF:

0.327

AC:

1684

AN:

5152

South Asian (SAS)

AF:

0.731

AC:

3523

AN:

4822

European-Finnish (FIN)

AF:

0.701

AC:

7397

AN:

10558

Middle Eastern (MID)

AF:

0.694

AC:

204

AN:

294

European-Non Finnish (NFE)

AF:

0.669

AC:

45460

AN:

67928

Other (OTH)

AF:

0.593

AC:

1252

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1773

3546

5318

7091

8864

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

770

1540

2310

3080

3850

<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:

0.647

Hom.:

92476

Bravo

AF:

0.587

Asia WGS

AF:

0.532

AC:

1853

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 02, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

-0.31

PromoterAI

0.074

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over