10-997529-C-T

Variant names:

• chr10-997529-C-T
• rs2242271
• NM_012341.3:c.561+221C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012341.3(GTPBP4):​c.561+221C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,180 control chromosomes in the GnomAD database, including 15,991 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 0.44 (15991 hom., cov: 34)
• Consequence: GTPBP4 NM_012341.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTPBP4	NM_012341.3	c.561+221C>T		intron_variant	Intron 5 of 16	ENST00000360803.9	NP_036473.2
GTPBP4	XM_047424932.1	c.420+221C>T		intron_variant	Intron 5 of 16		XP_047280888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTPBP4	ENST00000360803.9	c.561+221C>T		intron_variant	Intron 5 of 16	1	NM_012341.3	ENSP00000354040.4
GTPBP4	ENST00000491635.1	n.1440+221C>T		intron_variant	Intron 3 of 10	2
GTPBP4	ENST00000360059.5	c.*221C>T		downstream_gene_variant		5		ENSP00000353168.5

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67457 AN: 152062 Hom.: 15969 Cov.: 34

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.442

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.444 AC: 67501 AN: 152180 Hom.: 15991 Cov.: 34 AF XY: 0.449 AC XY: 33430 AN XY: 74404

African (AFR) AF: 0.271 AC: 11228 AN: 41500

American (AMR) AF: 0.487 AC: 7449 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1355 AN: 3470

East Asian (EAS) AF: 0.564 AC: 2923 AN: 5182

South Asian (SAS) AF: 0.554 AC: 2670 AN: 4820

European-Finnish (FIN) AF: 0.551 AC: 5842 AN: 10594

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34504 AN: 68020

Other (OTH) AF: 0.448 AC: 944 AN: 2108

Alfa AF: 0.474 Hom.: 21861

Bravo AF: 0.427

Asia WGS AF: 0.552 AC: 1917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.96
DANN	Benign	0.61
PhyloP100		-0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2242271; hg19: chr10-1043469;