rs200959196

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001042413.2(GLIS3):c.1154G>T(p.Gly385Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000288 in 1,574,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G385S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

GLIS3
NM_001042413.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:5

Conservation

PhyloP100: -0.450

Publications

1 publications found

Variant links:

Genes affected

GLIS3 (HGNC:28510): (GLIS family zinc finger 3) This gene is a member of the GLI-similar zinc finger protein family and encodes a nuclear protein with five C2H2-type zinc finger domains. This protein functions as both a repressor and activator of transcription and is specifically involved in the development of pancreatic beta cells, the thyroid, eye, liver and kidney. Mutations in this gene have been associated with neonatal diabetes and congenital hypothyroidism (NDH). Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only two have been determined. [provided by RefSeq, Jul 2008]

GLIS3 Gene-Disease associations (from GenCC):

neonatal diabetes mellitus with congenital hypothyroidism
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
Tourette syndrome
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

GLIS3 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=0.017202407).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042413.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLIS3	NM_001042413.2	MANE Select	c.1154G>T	p.Gly385Val	missense	Exon 4 of 11	NP_001035878.1	Q8NEA6-2
GLIS3	NM_001438906.1		c.1154G>T	p.Gly385Val	missense	Exon 4 of 11	NP_001425835.1
GLIS3	NM_001438907.1		c.1154G>T	p.Gly385Val	missense	Exon 4 of 11	NP_001425836.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLIS3	ENST00000381971.8	TSL:5 MANE Select	c.1154G>T	p.Gly385Val	missense	Exon 4 of 11	ENSP00000371398.3	Q8NEA6-2
GLIS3	ENST00000324333.14	TSL:1	c.689G>T	p.Gly230Val	missense	Exon 3 of 10	ENSP00000325494.10	Q8NEA6-1
GLIS3	ENST00000491889.6	TSL:1	n.*517G>T		non_coding_transcript_exon	Exon 3 of 10	ENSP00000419914.1	F8WEV9

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.000353

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000205

AC:

AN:

175834

AF XY:

0.000164

show subpopulations

Gnomad AFR exome

AF:

0.000111

Gnomad AMR exome

AF:

0.000248

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000356

Gnomad OTH exome

AF:

0.000419

GnomAD4 exome

AF:

0.000300

AC:

427

AN:

1422058

Hom.:

Cov.:

AF XY:

0.000291

AC XY:

205

AN XY:

704866

show subpopulations

African (AFR)

AF:

0.0000613

AC:

AN:

32606

American (AMR)

AF:

0.000202

AC:

AN:

39646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25444

East Asian (EAS)

AF:

0.00

AC:

AN:

37634

South Asian (SAS)

AF:

0.00

AC:

AN:

82866

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44188

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5628

European-Non Finnish (NFE)

AF:

0.000374

AC:

410

AN:

1095128

Other (OTH)

AF:

0.000102

AC:

AN:

58918

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

118

148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000177

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41474

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

68024

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

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:

0.000128

Hom.:

Bravo

AF:

0.000185

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000147

AC:

ExAC

AF:

0.000151

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Neonatal diabetes mellitus with congenital hypothyroidism (3)

Monogenic diabetes (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.1

(source)

DANN

Benign

0.30

DEOGEN2

Benign

0.063

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.29

M_CAP

Benign

0.0056

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.81

PhyloP100

-0.45

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.69

REVEL

Benign

0.052

Sift

Benign

0.17

Sift4G

Benign

0.66

Polyphen

0.0010

Vest4

0.16

MVP

0.36

MPC

0.029

ClinPred

0.011

GERP RS

2.4

Varity_R

0.043

gMVP

0.44

Mutation Taster

=96/4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over