rs9635649

Positions:

• chrX-312927-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GTPBP6	NM_012227.4	c.758-3T>C		splice_region_variant, intron_variant		ENST00000326153.10	NP_036359.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTPBP6	ENST00000326153.10	c.758-3T>C		splice_region_variant, intron_variant		1	NM_012227.4	ENSP00000316598.5

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2669 AN: 152198 Hom.: 87 Cov.: 34 AF XY: 0.0169 AC XY: 1257 AN XY: 74338

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

GnomAD3 exomes AF: 0.00441 AC: 1087 AN: 246372 Hom.: 28 AF XY: 0.00333 AC XY: 446 AN XY: 133742

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 SAS exome AF: 0.0000658

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.: 79 Cov.: 34 AF XY: 0.00159 AC XY: 1154 AN XY: 724316

Gnomad4 AFR exome AF: 0.0685

Gnomad4 AMR exome AF: 0.00308

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000244

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000541

Gnomad4 OTH exome AF: 0.00374

GnomAD4 genome AF: 0.0176 AC: 2679 AN: 152316 Hom.: 88 Cov.: 34 AF XY: 0.0170 AC XY: 1267 AN XY: 74466

Gnomad4 AFR AF: 0.0615

Gnomad4 AMR AF: 0.00516

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0128

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
DANN	Benign	0.41
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

LitVar

Other links and lift over

dbSNP: rs9635649; hg19: chrX-229594;