4-54100663-G-C

Variant names:

• chr4-54100663-G-C
• rs13144341
• NM_133267.3:c.319G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133267.3(GSX2):​c.319G>C​(p.Gly107Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. G107S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GSX2 NM_133267.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 17 publications found

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]

GSX2 Gene-Disease associations (from GenCC):

• diencephalic-mesencephalic junction dysplasia syndrome 2

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000282278 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11295506).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133267.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSX2	NM_133267.3	MANE Select	c.319G>C	p.Gly107Arg	missense	Exon 1 of 2	NP_573574.2	Q9BZM3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSX2	ENST00000326902.7	TSL:1 MANE Select	c.319G>C	p.Gly107Arg	missense	Exon 1 of 2	ENSP00000319118.2	Q9BZM3
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-174262G>C		intron	N/A	ENSP00000423325.1	A0A0B4J203
	GSX2	ENST00000503800.1	TSL:5	c.319G>C	p.Gly107Arg	missense	Exon 1 of 2	ENSP00000422213.1	D6R903

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.018
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.11
Sift	Uncertain	0.020	D
Sift4G	Benign	0.090	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.32		Loss of glycosylation at S111 (P = 0.0297)
MVP		0.61
MPC		1.1
ClinPred		0.62	D
GERP RS		1.4
PromoterAI		-0.015	Neutral
Varity_R		0.073
gMVP		0.39
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13144341; hg19: chr4-54966830;