dbSNP rs900683510: GYG2:p.Ala12Ser (chrX-2843024-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003918.3(GYG2):c.34G>T(p.Ala12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000602 in 498,749 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000052 ( 0 hom. 0 hem. )

Consequence

GYG2
NM_003918.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

Publications

0 publications found

Variant links:

Genes affected

GYG2 (HGNC:4700): (glycogenin 2) This gene encodes a member of the the glycogenin family. Glycogenin is a self-glucosylating protein involved in the initiation reactions of glycogen biosynthesis. A gene on chromosome 3 encodes the muscle glycogenin and this X-linked gene encodes the glycogenin mainly present in liver; both are involved in blood glucose homeostasis. This gene has a short version on chromosome Y, which is 3' truncated and can not make a functional protein. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, May 2010]

GYG2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09758443).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003918.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GYG2	NM_001079855.2	MANE Select	c.8-189G>T		intron	N/A	NP_001073324.1	O15488-2
GYG2	NM_003918.3		c.34G>T	p.Ala12Ser	missense	Exon 3 of 12	NP_003909.2	O15488-1
GYG2	NM_001184703.2		c.34G>T	p.Ala12Ser	missense	Exon 3 of 10	NP_001171632.1	O15488-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GYG2	ENST00000381163.7	TSL:1	c.34G>T	p.Ala12Ser	missense	Exon 3 of 12	ENSP00000370555.3	O15488-1
GYG2	ENST00000398806.8	TSL:1 MANE Select	c.8-189G>T		intron	N/A	ENSP00000381786.3	O15488-2
GYG2	ENST00000958345.1		c.34G>T	p.Ala12Ser	missense	Exon 3 of 12	ENSP00000628404.1

Frequencies

GnomAD3 genomes

AF:

0.00000904

AC:

AN:

110655

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000329

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000106

AC:

AN:

94055

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000543

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000515

AC:

AN:

388094

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

136212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12195

American (AMR)

AF:

0.0000763

AC:

AN:

26197

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13904

East Asian (EAS)

AF:

0.00

AC:

AN:

23183

South Asian (SAS)

AF:

0.00

AC:

AN:

35820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27292

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2177

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

225073

Other (OTH)

AF:

0.00

AC:

AN:

22253

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000904

AC:

AN:

110655

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32903

show subpopulations

African (AFR)

AF:

0.0000329

AC:

AN:

30380

American (AMR)

AF:

0.00

AC:

AN:

10381

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2634

East Asian (EAS)

AF:

0.00

AC:

AN:

3523

South Asian (SAS)

AF:

0.00

AC:

AN:

2596

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5865

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52869

Other (OTH)

AF:

0.00

AC:

AN:

1492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.6

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.00059

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.76

M_CAP

Benign

0.0021

MetaRNN

Benign

0.098

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

1.2

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.19

REVEL

Benign

0.022

Sift

Pathogenic

0.0

Sift4G

Benign

0.49

Polyphen

0.64

Vest4

0.080

MutPred

0.29

Gain of glycosylation at A12 (P = 0.0032)

MVP

0.35

MPC

0.048

ClinPred

0.13

GERP RS

0.50

PromoterAI

0.0046

Neutral

(source)

Varity_R

0.31

gMVP

0.26

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over