Genetic Variant NM_001394028.1:c.*149C>A (chr17-43952807-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001394028.1(PYY):c.*149C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 803,240 control chromosomes in the GnomAD database, including 9,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1691 hom., cov: 32)

Exomes 𝑓: 0.092 ( 7760 hom. )

Consequence

PYY
NM_001394028.1 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.79

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-43952807-G-T is Benign according to our data. Variant chr17-43952807-G-T is described in ClinVar as [Benign]. Clinvar id is 1249578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PYY	NM_001394028.1 link	c.*149C>A	3_prime_UTR_variant	Exon 4 of 4	ENST00000692052.1	NP_001380957.1
PYY	NM_004160.6 link	c.*149C>A	3_prime_UTR_variant	Exon 7 of 7		NP_004151.4	P10082-1
PYY	NM_001394029.1 link	c.*298C>A	3_prime_UTR_variant	Exon 3 of 3		NP_001380958.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PYY	ENST00000692052 link	c.*149C>A	3_prime_UTR_variant	Exon 4 of 4		NM_001394028.1	ENSP00000509262.1	P10082-1
PYY	ENST00000360085 link	c.*149C>A	3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000353198.1	P10082-1
PYY	ENST00000592796 link	c.*298C>A	3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000467310.1	P10082-2

Frequencies

GnomAD3 genomes

AF:

0.100

AC:

15234

AN:

152134

Hom.:

1681

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0869

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.0901

Gnomad EAS

AF:

0.596

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0474

Gnomad OTH

AF:

0.101

GnomAD4 exome

AF:

0.0923

AC:

60116

AN:

650988

Hom.:

7760

Cov.:

AF XY:

0.0944

AC XY:

31595

AN XY:

334810

show subpopulations

Gnomad4 AFR exome

AF:

0.0857

Gnomad4 AMR exome

AF:

0.215

Gnomad4 ASJ exome

AF:

0.0905

Gnomad4 EAS exome

AF:

0.599

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.105

Gnomad4 NFE exome

AF:

0.0452

Gnomad4 OTH exome

AF:

0.0993

GnomAD4 genome

AF:

0.100

AC:

15262

AN:

152252

Hom.:

1691

Cov.:

AF XY:

0.109

AC XY:

8144

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0871

Gnomad4 AMR

AF:

0.180

Gnomad4 ASJ

AF:

0.0901

Gnomad4 EAS

AF:

0.596

Gnomad4 SAS

AF:

0.181

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.0474

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.0322

Hom.:

Bravo

AF:

0.106

Asia WGS

AF:

0.362

AC:

1256

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 19820027) -

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

-0.82

CADD

Benign

0.82

DANN

Benign

0.73

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over