Genetic Variant GLCCI1:p.Ser5Ala (chr7-7969363-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_138426.4(GLCCI1):c.13T>G(p.Ser5Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000159 in 1,321,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

GLCCI1
NM_138426.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.633

Publications

0 publications found

Variant links:

Genes affected

GLCCI1 (HGNC:18713): (glucocorticoid induced 1) This gene encodes a protein of unknown function. Expression of this gene is induced by glucocorticoids and may be an early marker for glucocorticoid-induced apoptosis. Single nucleotide polymorphisms in this gene are associated with a decreased response to inhaled glucocorticoids in asthmatic patients. [provided by RefSeq, Feb 2012]

GLCCI1 links:

GLCCI1-DT (HGNC:40852): (GLCCI1 divergent transcript)

GLCCI1-DT links:

ENSG00000283549 (HGNC:):

ENSG00000283549 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044201255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLCCI1	NM_138426.4 link	c.13T>G	p.Ser5Ala	missense_variant	Exon 1 of 8	ENST00000223145.10	NP_612435.1	Q86VQ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GLCCI1	ENST00000223145.10 link	c.13T>G	p.Ser5Ala	missense_variant	Exon 1 of 8	1	NM_138426.4	ENSP00000223145.5	Q86VQ1
GLCCI1-DT	ENST00000428660.1 link	n.132+409A>C		intron_variant	Intron 1 of 1	4
ENSG00000283549	ENST00000469183.5 link	n.492-34545T>G		intron_variant	Intron 4 of 4	5
GLCCI1-DT	ENST00000837755.1 link	n.130+409A>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

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:

0.0000690

AC:

AN:

115934

AF XY:

0.0000908

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000392

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1171658

Hom.:

Cov.:

AF XY:

0.0000259

AC XY:

AN XY:

579276

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24192

American (AMR)

AF:

0.00

AC:

AN:

27194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18398

East Asian (EAS)

AF:

0.00

AC:

AN:

24238

South Asian (SAS)

AF:

0.000189

AC:

AN:

63378

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25140

Middle Eastern (MID)

AF:

0.000257

AC:

AN:

3894

European-Non Finnish (NFE)

AF:

0.00000532

AC:

AN:

939016

Other (OTH)

AF:

0.0000433

AC:

AN:

46208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000669

AC:

AN:

149546

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72924

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

40646

American (AMR)

AF:

0.0000661

AC:

AN:

15120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5052

South Asian (SAS)

AF:

0.00

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9996

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67226

Other (OTH)

AF:

0.00

AC:

AN:

2066

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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

ExAC

AF:

0.0000929

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 17, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.13T>G (p.S5A) alteration is located in exon 1 (coding exon 1) of the GLCCI1 gene. This alteration results from a T to G substitution at nucleotide position 13, causing the serine (S) at amino acid position 5 to be replaced by an alanine (A). 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

0.064

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.012

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.18

M_CAP

Benign

0.0012

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.46

PhyloP100

-0.63

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.21

REVEL

Benign

0.037

Sift

Pathogenic

0.0

Sift4G

Benign

0.16

Polyphen

0.22

Vest4

0.17

MutPred

0.18

Loss of phosphorylation at S5 (P = 2e-04);

MVP

0.26

MPC

0.32

ClinPred

0.18

PromoterAI

0.019

Neutral

(source)

Varity_R

0.36

gMVP

0.15

Mutation Taster

=97/3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over