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GeneBe

20-25274603-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002862.4(PYGB):c.540C>T(p.Ala180=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000256 in 1,613,174 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

PYGB
NM_002862.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -10.3
Variant links:
Genes affected
PYGB (HGNC:9723): (glycogen phosphorylase B) The protein encoded by this gene is a glycogen phosphorylase found predominantly in the brain. The encoded protein forms homodimers which can associate into homotetramers, the enzymatically active form of glycogen phosphorylase. The activity of this enzyme is positively regulated by AMP and negatively regulated by ATP, ADP, and glucose-6-phosphate. This enzyme catalyzes the rate-determining step in glycogen degradation. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.64).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-25274603-C-T is Benign according to our data. Variant chr20-25274603-C-T is described in ClinVar as [Benign]. Clinvar id is 713733.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=-10.3 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 GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PYGBNM_002862.4 linkuse as main transcriptc.540C>T p.Ala180= synonymous_variant 5/20 ENST00000216962.9
PYGBXM_047440342.1 linkuse as main transcriptc.540C>T p.Ala180= synonymous_variant 5/16

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PYGBENST00000216962.9 linkuse as main transcriptc.540C>T p.Ala180= synonymous_variant 5/201 NM_002862.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00138
AC:
210
AN:
152184
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00468
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000459
AC:
115
AN:
250524
Hom.:
2
AF XY:
0.000332
AC XY:
45
AN XY:
135494
show subpopulations
Gnomad AFR exome
AF:
0.00517
Gnomad AMR exome
AF:
0.000463
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000598
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.000138
AC:
202
AN:
1460872
Hom.:
1
Cov.:
31
AF XY:
0.000122
AC XY:
89
AN XY:
726752
show subpopulations
Gnomad4 AFR exome
AF:
0.00403
Gnomad4 AMR exome
AF:
0.000380
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00139
AC:
211
AN:
152302
Hom.:
1
Cov.:
33
AF XY:
0.00137
AC XY:
102
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.00469
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000916
Hom.:
0
Bravo
AF:
0.00163
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
Cadd
Benign
0.76
Dann
Benign
0.74
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs35481467; hg19: chr20-25255239; COSMIC: COSV53816203; API