Genetic Variant GTPBP6:c.758-3T>C (chrX-312927-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_012227.4(GTPBP6):c.758-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,609,324 control chromosomes in the GnomAD database, including 167 homozygotes. There are 2,421 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.018 ( 88 hom., 1267 hem., cov: 34)

Exomes 𝑓: 0.0019 ( 79 hom. 1154 hem. )

Consequence

GTPBP6
NM_012227.4 splice_region, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.402

Publications

0 publications found

Variant links:

Genes affected

GTPBP6 (HGNC:30189): (GTP binding protein 6 (putative)) This gene encodes a GTP binding protein and is located in the pseudoautosomal region (PAR) at the end of the short arms of the X and Y chromosomes. [provided by RefSeq, Nov 2011]

GTPBP6 links:

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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=-0.76).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTPBP6	NM_012227.4 link	c.758-3T>C		splice_region_variant, intron_variant	Intron 5 of 9	ENST00000326153.10	NP_036359.3	O43824

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTPBP6	ENST00000326153.10 link	c.758-3T>C		splice_region_variant, intron_variant	Intron 5 of 9	1	NM_012227.4	ENSP00000316598.5		O43824
GTPBP6	ENST00000850592.1 link	c.758-3T>C		splice_region_variant, intron_variant	Intron 5 of 9			ENSP00000520879.1

Frequencies

GnomAD3 genomes

AF:

0.0175

AC:

2669

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0614

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0129

GnomAD2 exomes

AF:

0.00441

AC:

1087

AN:

246372

AF XY:

0.00333

show subpopulations

Gnomad AFR exome

AF:

0.0632

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.00217

GnomAD4 exome

AF:

0.00188

AC:

2737

AN:

1457008

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1154

AN XY:

724316

show subpopulations

African (AFR)

AF:

0.0685

AC:

2282

AN:

33330

American (AMR)

AF:

0.00308

AC:

137

AN:

44448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25910

East Asian (EAS)

AF:

0.00

AC:

AN:

39638

South Asian (SAS)

AF:

0.000244

AC:

AN:

86036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53288

Middle Eastern (MID)

AF:

0.00241

AC:

AN:

4978

European-Non Finnish (NFE)

AF:

0.0000541

AC:

AN:

1109290

Other (OTH)

AF:

0.00374

AC:

225

AN:

60090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

138

275

413

550

688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.0176

AC:

2679

AN:

152316

Hom.:

Cov.:

AF XY:

0.0170

AC XY:

1267

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0615

AC:

2555

AN:

41576

American (AMR)

AF:

0.00516

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68022

Other (OTH)

AF:

0.0128

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

131

263

394

526

657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Bravo

AF:

0.0198

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.15

(source)

DANN

Benign

0.41

PhyloP100

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over