Variant 13-27792965-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_145657.3(GSX1):c.275A>G(p.His92Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00024 in 1,546,982 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 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

GSX1
NM_145657.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

Variant links:

Genes affected

GSX1 (HGNC:20374): (GS homeobox 1) Enables sequence-specific double-stranded DNA binding activity. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

GSX1 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=0.39369196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSX1	NM_145657.3 linkuse as main transcript	c.275A>G	p.His92Arg	missense_variant	1/2	ENST00000302945.3	NP_663632.1	Q9H4S2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSX1	ENST00000302945.3 linkuse as main transcript	c.275A>G	p.His92Arg	missense_variant	1/2	1	NM_145657.3	ENSP00000304331.2		Q9H4S2

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

144412

Hom.:

AF XY:

0.000100

AC XY:

AN XY:

79702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000786

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:

0.000210

Gnomad OTH exome

AF:

0.000235

GnomAD4 exome

AF:

0.000252

AC:

351

AN:

1394768

Hom.:

Cov.:

AF XY:

0.000236

AC XY:

163

AN XY:

689520

show subpopulations

Gnomad4 AFR exome

AF:

0.0000934

Gnomad4 AMR exome

AF:

0.0000817

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:

0.000310

Gnomad4 OTH exome

AF:

0.000154

GnomAD4 genome

AF:

0.000131

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000117

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.0000828

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

Oct 13, 2021

The c.275A>G (p.H92R) alteration is located in exon 1 (coding exon 1) of the GSX1 gene. This alteration results from a A to G substitution at nucleotide position 275, causing the histidine (H) at amino acid position 92 to be replaced by an arginine (R). 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

0.17

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.34

Eigen

Benign

0.049

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.39

MetaSVM

Uncertain

0.020

MutationAssessor

Uncertain

2.2

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.53

Sift

Benign

0.42

Sift4G

Benign

0.55

Polyphen

0.60

Vest4

0.27

MVP

0.96

MPC

0.98

ClinPred

0.10

GERP RS

4.1

Varity_R

0.25

gMVP

0.70

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.

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