chr4-54100500-C-T

Variant names:

• chr4-54100500-C-T
• rs3194383
• NM_133267.3:c.156C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_133267.3(GSX2):​c.156C>T​(p.Ser52Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 1,613,098 control chromosomes in the GnomAD database, including 312,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24934 hom., cov: 31)
  • Exomes 𝑓: 0.62 (287701 hom.)
• Consequence: GSX2 NM_133267.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.380
• Publications: 12 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 4-54100500-C-T is Benign according to our data. Variant chr4-54100500-C-T is described in ClinVar as Benign. ClinVar VariationId is 1182813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

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.156C>T	p.Ser52Ser	synonymous	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.156C>T	p.Ser52Ser	synonymous	Exon 1 of 2	ENSP00000319118.2	Q9BZM3
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-174425C>T		intron	N/A	ENSP00000423325.1	A0A0B4J203
	GSX2	ENST00000503800.1	TSL:5	c.156C>T	p.Ser52Ser	synonymous	Exon 1 of 2	ENSP00000422213.1	D6R903

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84166 AN: 151816 Hom.: 24920 Cov.: 31

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.566

GnomAD2 exomes AF: 0.641 AC: 159009 AN: 248174 AF XY: 0.640

Gnomad AFR exome AF: 0.330

Gnomad AMR exome AF: 0.774

Gnomad ASJ exome AF: 0.557

Gnomad EAS exome AF: 0.834

Gnomad FIN exome AF: 0.643

Gnomad NFE exome AF: 0.621

Gnomad OTH exome AF: 0.636

GnomAD4 exome AF: 0.624 AC: 911193 AN: 1461164 Hom.: 287701 Cov.: 72 AF XY: 0.624 AC XY: 453771 AN XY: 726900

African (AFR) AF: 0.326 AC: 10912 AN: 33474

American (AMR) AF: 0.762 AC: 34047 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 14487 AN: 26104

East Asian (EAS) AF: 0.825 AC: 32740 AN: 39680

South Asian (SAS) AF: 0.636 AC: 54824 AN: 86192

European-Finnish (FIN) AF: 0.647 AC: 34396 AN: 53132

Middle Eastern (MID) AF: 0.583 AC: 3361 AN: 5768

European-Non Finnish (NFE) AF: 0.620 AC: 689059 AN: 1111766

Other (OTH) AF: 0.619 AC: 37367 AN: 60368

GnomAD4 genome AF: 0.554 AC: 84195 AN: 151934 Hom.: 24934 Cov.: 31 AF XY: 0.560 AC XY: 41578 AN XY: 74266

African (AFR) AF: 0.340 AC: 14082 AN: 41456

American (AMR) AF: 0.668 AC: 10205 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1919 AN: 3466

East Asian (EAS) AF: 0.830 AC: 4235 AN: 5100

South Asian (SAS) AF: 0.648 AC: 3117 AN: 4808

European-Finnish (FIN) AF: 0.644 AC: 6804 AN: 10572

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41821 AN: 67932

Other (OTH) AF: 0.568 AC: 1197 AN: 2106

Alfa AF: 0.588 Hom.: 17932

Bravo AF: 0.549

Asia WGS AF: 0.695 AC: 2416 AN: 3478

EpiCase AF: 0.610

EpiControl AF: 0.611

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Diencephalic-mesencephalic junction dysplasia syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		-0.38
PromoterAI		0.14	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3194383; hg19: chr4-54966667; COSMIC: COSV58842352; COSMIC: COSV58842352;