NM_002862.4:c.16A>C

Variant names:

• chr20-25248194-A-C
• rs2092876085
• NM_002862.4:c.16A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002862.4(PYGB):​c.16A>C​(p.Thr6Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,439,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: PYGB NM_002862.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.391
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40378347).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002862.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYGB	NM_002862.4	MANE Select	c.16A>C	p.Thr6Pro	missense	Exon 1 of 20	NP_002853.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYGB	ENST00000216962.9	TSL:1 MANE Select	c.16A>C	p.Thr6Pro	missense	Exon 1 of 20	ENSP00000216962.3	P11216
	PYGB	ENST00000896654.1		c.16A>C	p.Thr6Pro	missense	Exon 1 of 21	ENSP00000566713.1
	PYGB	ENST00000944638.1		c.16A>C	p.Thr6Pro	missense	Exon 1 of 21	ENSP00000614697.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000278 AC: 4 AN: 1439072 Hom.: 0 Cov.: 32 AF XY: 0.00000419 AC XY: 3 AN XY: 715374

African (AFR) AF: 0.00 AC: 0 AN: 31376

American (AMR) AF: 0.00 AC: 0 AN: 42038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25598

East Asian (EAS) AF: 0.0000267 AC: 1 AN: 37496

South Asian (SAS) AF: 0.0000239 AC: 2 AN: 83680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101372

Other (OTH) AF: 0.0000168 AC: 1 AN: 59580

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.71	D
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Benign	1.4	L
PhyloP100		0.39
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.031	D
Polyphen		0.37	B
Vest4		0.31
MutPred		0.23		Gain of glycosylation at T6 (P = 0.0235)
MVP		0.89
MPC		0.41
ClinPred		0.93	D
GERP RS		3.9
PromoterAI		-0.10	Neutral
Varity_R		0.39
gMVP		0.50
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs2092876085; hg19: chr20-25228830;