1-53509949-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001367484.1(GLIS1):ā€‹c.1962G>Cā€‹(p.Gln654His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000691 in 1,303,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000061 ( 0 hom. )

Consequence

GLIS1
NM_001367484.1 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.038720965).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GLIS1NM_001367484.1 linkuse as main transcriptc.1962G>C p.Gln654His missense_variant 9/11 ENST00000628545.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GLIS1ENST00000628545.2 linkuse as main transcriptc.1962G>C p.Gln654His missense_variant 9/115 NM_001367484.1 P2
GLIS1ENST00000312233.4 linkuse as main transcriptc.1437G>C p.Gln479His missense_variant 8/102 A2

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152060
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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
GnomAD3 exomes
AF:
0.0000507
AC:
5
AN:
98662
Hom.:
0
AF XY:
0.0000379
AC XY:
2
AN XY:
52736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000488
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:
0.0000188
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000608
AC:
7
AN:
1151268
Hom.:
0
Cov.:
32
AF XY:
0.00000545
AC XY:
3
AN XY:
550000
show subpopulations
Gnomad4 AFR exome
AF:
0.0000403
Gnomad4 AMR exome
AF:
0.000248
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:
0.00000105
Gnomad4 OTH exome
AF:
0.0000218
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152060
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74260
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000352
AC:
4

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 submitterclinical testingAmbry GeneticsFeb 17, 2022The c.1437G>C (p.Q479H) alteration is located in exon 8 (coding exon 6) of the GLIS1 gene. This alteration results from a G to C substitution at nucleotide position 1437, causing the glutamine (Q) at amino acid position 479 to be replaced by a histidine (H). 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
0.14
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
15
DANN
Benign
0.41
DEOGEN2
Benign
0.026
T;.
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.41
N
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.0076
T
MetaRNN
Benign
0.039
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L;.
MutationTaster
Benign
0.97
N
PrimateAI
Benign
0.48
T
PROVEAN
Benign
0.51
N;.
REVEL
Benign
0.060
Sift
Benign
0.15
T;.
Sift4G
Benign
0.57
T;T
Polyphen
0.0
B;.
Vest4
0.19
MutPred
0.28
Gain of glycosylation at S478 (P = 0.0704);.;
MVP
0.38
MPC
0.33
ClinPred
0.063
T
GERP RS
3.0
Varity_R
0.049
gMVP
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs762704926; hg19: chr1-53975622; API