Variant chr16-74459783-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001145667.2(GLG1):c.3043A>G(p.Ser1015Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000108 in 1,581,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

GLG1
NM_001145667.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60

Variant links:

Genes affected

GLG1 (HGNC:4316): (golgi glycoprotein 1) Predicted to enable fibroblast growth factor binding activity. Predicted to act upstream of or within several processes, including negative regulation of protein processing; negative regulation of transforming growth factor beta receptor signaling pathway; and regulation of chondrocyte differentiation. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

GLG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18873575).

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLG1	NM_001145667.2 linkuse as main transcript	c.3043A>G	p.Ser1015Gly	missense_variant	23/26	ENST00000422840.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLG1	ENST00000422840.7 linkuse as main transcript	c.3043A>G	p.Ser1015Gly	missense_variant	23/26	1	NM_001145667.2	P2	Q92896-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

241950

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

131000

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000360

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000105

AC:

AN:

1429254

Hom.:

Cov.:

AF XY:

0.00000982

AC XY:

AN XY:

713114

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:

0.0000138

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2023

The c.3043A>G (p.S1015G) alteration is located in exon 23 (coding exon 23) of the GLG1 gene. This alteration results from a A to G substitution at nucleotide position 3043, causing the serine (S) at amino acid position 1015 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

.;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

0.0046

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L;.

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.055

Sift

Benign

0.33

T;T;T

Sift4G

Benign

0.16

T;T;T

Polyphen

0.11

B;B;.

Vest4

0.28

MutPred

0.42

Gain of glycosylation at S1014 (P = 0.0266);Gain of glycosylation at S1014 (P = 0.0266);.;

MVP

0.22

MPC

0.50

ClinPred

0.23

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.094

gMVP

0.21

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