10-1000772-G-A

Variant names:

• chr10-1000772-G-A
• rs2306409
• NM_012341.3:c.750G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012341.3(GTPBP4):​c.750G>A​(p.Ala250Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 1,607,090 control chromosomes in the GnomAD database, including 228,395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (19788 hom., cov: 29)
  • Exomes 𝑓: 0.53 (208607 hom.)
• Consequence: GTPBP4 NM_012341.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.31

Genes affected

GTPBP4 (HGNC:21535): (GTP binding protein 4) GTP-binding proteins are GTPases and function as molecular switches that can flip between two states: active, when GTP is bound, and inactive, when GDP is bound. 'Active' in this context usually means that the molecule acts as a signal to trigger other events in the cell. When an extracellular ligand binds to a G-protein-linked receptor, the receptor changes its conformation and switches on the trimeric G proteins that associate with it by causing them to eject their GDP and replace it with GTP. The switch is turned off when the G protein hydrolyzes its own bound GTP, converting it back to GDP. But before that occurs, the active protein has an opportunity to diffuse away from the receptor and deliver its message for a prolonged period to its downstream target. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-1000772-G-A is Benign according to our data. Variant chr10-1000772-G-A is described in ClinVar as [Benign]. Clinvar id is 1263198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTPBP4	NM_012341.3	c.750G>A	p.Ala250Ala	synonymous_variant	Exon 7 of 17	ENST00000360803.9	NP_036473.2
GTPBP4	XM_047424932.1	c.609G>A	p.Ala203Ala	synonymous_variant	Exon 7 of 17		XP_047280888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTPBP4	ENST00000360803.9	c.750G>A	p.Ala250Ala	synonymous_variant	Exon 7 of 17	1	NM_012341.3	ENSP00000354040.4
GTPBP4	ENST00000491635.1	n.1629G>A		non_coding_transcript_exon_variant	Exon 5 of 11	2

Frequencies

GnomAD3 genomes AF: 0.508 AC: 76912 AN: 151508 Hom.: 19761 Cov.: 29

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.504

GnomAD2 exomes AF: 0.534 AC: 131738 AN: 246514 AF XY: 0.537

Gnomad AFR exome AF: 0.423

Gnomad AMR exome AF: 0.545

Gnomad ASJ exome AF: 0.444

Gnomad EAS exome AF: 0.580

Gnomad FIN exome AF: 0.556

Gnomad NFE exome AF: 0.528

Gnomad OTH exome AF: 0.530

GnomAD4 exome AF: 0.534 AC: 776926 AN: 1455462 Hom.: 208607 Cov.: 35 AF XY: 0.536 AC XY: 387946 AN XY: 723434

Gnomad4 AFR exome AF: 0.423 AC: 14114 AN: 33338

Gnomad4 AMR exome AF: 0.547 AC: 24088 AN: 44050

Gnomad4 ASJ exome AF: 0.449 AC: 11560 AN: 25758

Gnomad4 EAS exome AF: 0.621 AC: 24591 AN: 39584

Gnomad4 SAS exome AF: 0.595 AC: 50628 AN: 85134

Gnomad4 FIN exome AF: 0.558 AC: 29688 AN: 53236

Gnomad4 NFE exome AF: 0.530 AC: 587175 AN: 1108488

Gnomad4 Remaining exome AF: 0.533 AC: 32043 AN: 60136

GnomAD4 genome AF: 0.508 AC: 76970 AN: 151628 Hom.: 19788 Cov.: 29 AF XY: 0.512 AC XY: 37915 AN XY: 74076

Gnomad4 AFR AF: 0.432 AC: 0.431769 AN: 0.431769

Gnomad4 AMR AF: 0.523 AC: 0.523459 AN: 0.523459

Gnomad4 ASJ AF: 0.457 AC: 0.456697 AN: 0.456697

Gnomad4 EAS AF: 0.593 AC: 0.592715 AN: 0.592715

Gnomad4 SAS AF: 0.606 AC: 0.606334 AN: 0.606334

Gnomad4 FIN AF: 0.569 AC: 0.56931 AN: 0.56931

Gnomad4 NFE AF: 0.530 AC: 0.529946 AN: 0.529946

Gnomad4 OTH AF: 0.510 AC: 0.509515 AN: 0.509515

Alfa AF: 0.519 Hom.: 40247

Bravo AF: 0.497

Asia WGS AF: 0.604 AC: 2101 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Oct 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.0050
DANN	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs2306409; hg19: chr10-1046712; COSMIC: COSV62552012; COSMIC: COSV62552012;