Genetic Variant NM_145657.3:c.412+36G>C (chr13-27793138-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.515

Publications

6 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145657.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSX1	NM_145657.3	MANE Select	c.412+36G>C		intron	N/A	NP_663632.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSX1	ENST00000302945.3	TSL:1 MANE Select	c.412+36G>C		intron	N/A	ENSP00000304331.2

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54092

AN:

151942

Hom.:

9832

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.381

AC:

41793

AN:

109828

AF XY:

0.367

show subpopulations

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 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.:

AF XY:

0.343

AC XY:

222792

AN XY:

650220

show subpopulations

African (AFR)

AF:

0.382

AC:

10990

AN:

28756

American (AMR)

AF:

0.539

AC:

16069

AN:

29814

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

5298

AN:

20106

East Asian (EAS)

AF:

0.338

AC:

12006

AN:

35570

South Asian (SAS)

AF:

0.266

AC:

18297

AN:

68682

European-Finnish (FIN)

AF:

0.387

AC:

12659

AN:

32740

Middle Eastern (MID)

AF:

0.209

AC:

1081

AN:

5180

European-Non Finnish (NFE)

AF:

0.347

AC:

365223

AN:

1053350

Other (OTH)

AF:

0.331

AC:

18257

AN:

55154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

15743

31486

47230

62973

78716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12296

24592

36888

49184

61480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.356

AC:

54173

AN:

152060

Hom.:

9865

Cov.:

AF XY:

0.358

AC XY:

26577

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.382

AC:

15864

AN:

41496

American (AMR)

AF:

0.430

AC:

6572

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

921

AN:

3472

East Asian (EAS)

AF:

0.319

AC:

1644

AN:

5148

South Asian (SAS)

AF:

0.264

AC:

1268

AN:

4812

European-Finnish (FIN)

AF:

0.389

AC:

4112

AN:

10580

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.334

AC:

22720

AN:

67944

Other (OTH)

AF:

0.313

AC:

662

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1807

3614

5421

7228

9035

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.3

(source)

DANN

Benign

0.51

PhyloP100

-0.52

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over