11-64751970-A-T

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong

The NM_005609.4(PYGM):​c.1722T>A​(p.Tyr574*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PYGM
NM_005609.4 stop_gained

Scores

2
2
3

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:2

Conservation

PhyloP100: 1.23
Variant links:
Genes affected
PYGM (HGNC:9726): (glycogen phosphorylase, muscle associated) This gene encodes a muscle enzyme involved in glycogenolysis. Highly similar enzymes encoded by different genes are found in liver and brain. Mutations in this gene are associated with McArdle disease (myophosphorylase deficiency), a glycogen storage disease of muscle. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Sep 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 18 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 11-64751970-A-T is Pathogenic according to our data. Variant chr11-64751970-A-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 871582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PYGMNM_005609.4 linkc.1722T>A p.Tyr574* stop_gained 14/20 ENST00000164139.4 NP_005600.1 P11217-1
PYGMNM_001164716.1 linkc.1458T>A p.Tyr486* stop_gained 12/18 NP_001158188.1 P11217-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PYGMENST00000164139.4 linkc.1722T>A p.Tyr574* stop_gained 14/201 NM_005609.4 ENSP00000164139.3 P11217-1
PYGMENST00000377432.7 linkc.1458T>A p.Tyr486* stop_gained 12/182 ENSP00000366650.3 P11217-2
PYGMENST00000462303.1 linkn.46T>A non_coding_transcript_exon_variant 1/32

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461426
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727070
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Glycogen storage disease, type V Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsMar 05, 2024- -
not provided Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJun 01, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.51
D
BayesDel_noAF
Pathogenic
0.50
CADD
Pathogenic
35
DANN
Uncertain
0.99
Eigen
Uncertain
0.27
Eigen_PC
Benign
0.039
FATHMM_MKL
Benign
0.73
D
Vest4
0.95
GERP RS
-4.4

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs119103260; hg19: chr11-64519442; API