rs2306409

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-1000772-G-A
• chr10-1000772-G-C

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
• Publications: 29 publications found

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012341.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTPBP4	NM_012341.3	MANE Select	c.750G>A	p.Ala250Ala	synonymous	Exon 7 of 17	NP_036473.2	Q9BZE4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTPBP4	ENST00000360803.9	TSL:1 MANE Select	c.750G>A	p.Ala250Ala	synonymous	Exon 7 of 17	ENSP00000354040.4	Q9BZE4-1
	GTPBP4	ENST00000925422.1		c.786G>A	p.Ala262Ala	synonymous	Exon 8 of 18	ENSP00000595481.1
	GTPBP4	ENST00000925423.1		c.750G>A	p.Ala250Ala	synonymous	Exon 7 of 17	ENSP00000595482.1

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

African (AFR) AF: 0.423 AC: 14114 AN: 33338

American (AMR) AF: 0.547 AC: 24088 AN: 44050

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 11560 AN: 25758

East Asian (EAS) AF: 0.621 AC: 24591 AN: 39584

South Asian (SAS) AF: 0.595 AC: 50628 AN: 85134

European-Finnish (FIN) AF: 0.558 AC: 29688 AN: 53236

Middle Eastern (MID) AF: 0.530 AC: 3039 AN: 5738

European-Non Finnish (NFE) AF: 0.530 AC: 587175 AN: 1108488

Other (OTH) 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

African (AFR) AF: 0.432 AC: 17845 AN: 41330

American (AMR) AF: 0.523 AC: 7966 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1582 AN: 3464

East Asian (EAS) AF: 0.593 AC: 3043 AN: 5134

South Asian (SAS) AF: 0.606 AC: 2891 AN: 4768

European-Finnish (FIN) AF: 0.569 AC: 5988 AN: 10518

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 35978 AN: 67890

Other (OTH) AF: 0.510 AC: 1071 AN: 2102

Alfa AF: 0.519 Hom.: 40247

Bravo AF: 0.497

Asia WGS AF: 0.604 AC: 2101 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.0050
DANN	Benign	0.35
PhyloP100		-2.3
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

Other links and lift over

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