13-27793138-G-C

Variant names:

• chr13-27793138-G-C
• rs3742112
• NM_145657.3:c.412+36G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145657.3(GSX1):​c.412+36G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,481,412 control chromosomes in the GnomAD database, including 90,683 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (9865 hom., cov: 32)
  • Exomes 𝑓: 0.35 (80818 hom.)
• Consequence: GSX1 NM_145657.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSX1	NM_145657.3	c.412+36G>C		intron_variant	Intron 1 of 1	ENST00000302945.3	NP_663632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSX1	ENST00000302945.3	c.412+36G>C		intron_variant	Intron 1 of 1	1	NM_145657.3	ENSP00000304331.2

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54092 AN: 151942 Hom.: 9832 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.316

GnomAD3 exomes AF: 0.381 AC: 41793 AN: 109828 Hom.: 8110 AF XY: 0.367 AC XY: 22148 AN XY: 60302

Gnomad AFR exome AF: 0.391

Gnomad AMR exome AF: 0.570

Gnomad ASJ exome AF: 0.279

Gnomad EAS exome AF: 0.331

Gnomad SAS exome AF: 0.288

Gnomad FIN exome AF: 0.406

Gnomad NFE exome AF: 0.345

Gnomad OTH exome AF: 0.362

GnomAD4 exome AF: 0.346 AC: 459880 AN: 1329352 Hom.: 80818 Cov.: 32 AF XY: 0.343 AC XY: 222792 AN XY: 650220

Gnomad4 AFR exome AF: 0.382

Gnomad4 AMR exome AF: 0.539

Gnomad4 ASJ exome AF: 0.264

Gnomad4 EAS exome AF: 0.338

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.387

Gnomad4 NFE exome AF: 0.347

Gnomad4 OTH exome AF: 0.331

GnomAD4 genome AF: 0.356 AC: 54173 AN: 152060 Hom.: 9865 Cov.: 32 AF XY: 0.358 AC XY: 26577 AN XY: 74330

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.313

Alfa AF: 0.317 Hom.: 1576

Bravo AF: 0.364

Asia WGS AF: 0.274 AC: 952 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.51

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: rs3742112; hg19: chr13-28367275; COSMIC: COSV104407345;