10-996883-C-A

Variant names:

• chr10-996883-C-A
• rs7918118
• NM_012341.3:c.461-325C>A

Variant summary

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

The NM_012341.3(GTPBP4):​c.461-325C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 291,188 control chromosomes in the GnomAD database, including 84,649 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 0.77 (45140 hom., cov: 31)
  • Exomes 𝑓: 0.75 (39509 hom.)
• Consequence: GTPBP4 NM_012341.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTPBP4	NM_012341.3	MANE Select	c.461-325C>A		intron	N/A	NP_036473.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTPBP4	ENST00000360803.9	TSL:1 MANE Select	c.461-325C>A		intron	N/A	ENSP00000354040.4
	GTPBP4	ENST00000491635.1	TSL:2	n.1015C>A		non_coding_transcript_exon	Exon 3 of 11
	GTPBP4	ENST00000360059.5	TSL:5	c.320-325C>A		intron	N/A	ENSP00000353168.5

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116579 AN: 151972 Hom.: 45096 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.793

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.740

GnomAD4 exome AF: 0.750 AC: 104334 AN: 139098 Hom.: 39509 Cov.: 0 AF XY: 0.754 AC XY: 55687 AN XY: 73812

African (AFR) AF: 0.839 AC: 2134 AN: 2542

American (AMR) AF: 0.807 AC: 2994 AN: 3712

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2629 AN: 3968

East Asian (EAS) AF: 0.920 AC: 4284 AN: 4656

South Asian (SAS) AF: 0.812 AC: 17050 AN: 21004

European-Finnish (FIN) AF: 0.814 AC: 6053 AN: 7436

Middle Eastern (MID) AF: 0.756 AC: 452 AN: 598

European-Non Finnish (NFE) AF: 0.720 AC: 63001 AN: 87468

Other (OTH) AF: 0.744 AC: 5737 AN: 7714

GnomAD4 genome AF: 0.767 AC: 116678 AN: 152090 Hom.: 45140 Cov.: 31 AF XY: 0.773 AC XY: 57519 AN XY: 74374

African (AFR) AF: 0.828 AC: 34368 AN: 41492

American (AMR) AF: 0.774 AC: 11824 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2295 AN: 3470

East Asian (EAS) AF: 0.896 AC: 4646 AN: 5186

South Asian (SAS) AF: 0.817 AC: 3926 AN: 4808

European-Finnish (FIN) AF: 0.827 AC: 8764 AN: 10592

Middle Eastern (MID) AF: 0.805 AC: 235 AN: 292

European-Non Finnish (NFE) AF: 0.712 AC: 48345 AN: 67942

Other (OTH) AF: 0.743 AC: 1573 AN: 2116

Alfa AF: 0.739 Hom.: 30673

Bravo AF: 0.766

Asia WGS AF: 0.854 AC: 2969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.75
DANN	Benign	0.51
PhyloP100		-0.15
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: rs7918118; hg19: chr10-1042823;