Variant 1-53510013-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001367484.1(GLIS1):c.1898T>C(p.Leu633Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000236 in 1,272,700 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

GLIS1
NM_001367484.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

Variant links:

Genes affected

GLIS1 (HGNC:29525): (GLIS family zinc finger 1) GLIS1 is a GLI (MIM 165220)-related Kruppel-like zinc finger protein that functions as an activator and repressor of transcription (Kim et al., 2002 [PubMed 12042312]).[supplied by OMIM, Mar 2008]

GLIS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41616243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIS1	NM_001367484.1 linkuse as main transcript	c.1898T>C	p.Leu633Pro	missense_variant	9/11	ENST00000628545.2	NP_001354413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLIS1	ENST00000628545.2 linkuse as main transcript	c.1898T>C	p.Leu633Pro	missense_variant	9/11	5	NM_001367484.1	ENSP00000486112.1		A0A0D9SEX9
GLIS1	ENST00000312233.4 linkuse as main transcript	c.1373T>C	p.Leu458Pro	missense_variant	8/10	2		ENSP00000309653.2		Q8NBF1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152032

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:

0.000193

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

GnomAD4 exome

AF:

0.00000178

AC:

AN:

1120668

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

531950

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000696

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000178

AC:

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

Jun 07, 2023

The c.1373T>C (p.L458P) alteration is located in exon 8 (coding exon 6) of the GLIS1 gene. This alteration results from a T to C substitution at nucleotide position 1373, causing the leucine (L) at amino acid position 458 to be replaced by a proline (P). 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

0.19

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

T;.

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.42

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.71

N;.

REVEL

Benign

0.11

Sift

Uncertain

0.0030

D;.

Sift4G

Benign

0.12

T;T

Polyphen

1.0

D;.

Vest4

0.57

MutPred

0.21

Gain of glycosylation at L458 (P = 0.0494);.;

MVP

0.37

MPC

0.41

ClinPred

0.88

GERP RS

4.3

Varity_R

0.28

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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