13-27792767-C-T

Position:

• chr13-27792767-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145657.3(GSX1):​c.77C>T​(p.Pro26Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSX1 NM_145657.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSX1	NM_145657.3	c.77C>T	p.Pro26Leu	missense_variant	1/2	ENST00000302945.3	NP_663632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSX1	ENST00000302945.3	c.77C>T	p.Pro26Leu	missense_variant	1/2	1	NM_145657.3	ENSP00000304331.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1336430 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 658982

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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 Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2024

The c.77C>T (p.P26L) alteration is located in exon 1 (coding exon 1) of the GSX1 gene. This alteration results from a C to T substitution at nucleotide position 77, causing the proline (P) at amino acid position 26 to be replaced by a leucine (L). 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	0.12
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.97	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	0.46	D
MutationAssessor	Uncertain	2.2	M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.95	N
REVEL	Uncertain	0.52
Sift	Benign	0.066	T
Sift4G	Benign	0.69	T
Polyphen		0.99	D
Vest4		0.31
MutPred		0.37		Gain of catalytic residue at P26 (P = 0);
MVP		0.97
MPC		0.88
ClinPred		0.89	D
GERP RS		4.0
Varity_R		0.17
gMVP		0.49

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

Other links and lift over

dbSNP: rs1410461001; hg19: chr13-28366904;