4-54100714-C-G

Variant summary

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

The NM_133267.3(GSX2):​c.370C>G​(p.His124Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000194 in 1,548,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H124N) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

GSX2
NM_133267.3 missense

Scores

2
6
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.882
Variant links:
Genes affected
GSX2 (HGNC:24959): (GS homeobox 2) Enables DNA-binding transcription factor activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including nervous system development; positive regulation of Notch signaling pathway; and regulation of respiratory gaseous exchange by nervous system process. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2910695).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GSX2NM_133267.3 linkc.370C>G p.His124Asp missense_variant Exon 1 of 2 ENST00000326902.7 NP_573574.2 Q9BZM3B2LYG3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GSX2ENST00000326902.7 linkc.370C>G p.His124Asp missense_variant Exon 1 of 2 1 NM_133267.3 ENSP00000319118.2 Q9BZM3
ENSG00000282278ENST00000507166.5 linkc.1018-174211C>G intron_variant Intron 12 of 23 2 ENSP00000423325.1 A0A0B4J203
GSX2ENST00000503800.1 linkc.363+7C>G splice_region_variant, intron_variant Intron 1 of 1 5 ENSP00000422213.1 D6R903
GSX2ENST00000507839.1 linkn.115-868C>G intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152104
Hom.:
0
Cov.:
33
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000204
AC:
3
AN:
146834
Hom.:
0
AF XY:
0.0000127
AC XY:
1
AN XY:
78634
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000816
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:
0.00
Gnomad OTH exome
AF:
0.000235
GnomAD4 exome
AF:
0.00000143
AC:
2
AN:
1396636
Hom.:
0
Cov.:
47
AF XY:
0.00000145
AC XY:
1
AN XY:
688888
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000562
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152104
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74288
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Uncertain
0.023
T
BayesDel_noAF
Uncertain
-0.080
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
T;T
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.28
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.51
T;.
M_CAP
Pathogenic
0.58
D
MetaRNN
Benign
0.29
T;T
MetaSVM
Benign
-0.33
T
MutationAssessor
Benign
1.8
L;L
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-0.81
.;N
REVEL
Uncertain
0.51
Sift
Uncertain
0.013
.;D
Sift4G
Benign
0.073
T;T
Polyphen
0.063
B;B
Vest4
0.37
MutPred
0.32
Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP
0.82
MPC
2.1
ClinPred
0.62
D
GERP RS
3.3
Varity_R
0.27
gMVP
0.33

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.

Other links and lift over

dbSNP: rs758503759; hg19: chr4-54966881; API