rs750227225

Variant names:

• chr22-38726085-C-T
• rs750227225
• NM_004286.5:c.1153C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004286.5(GTPBP1):​c.1153C>T​(p.Pro385Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,613,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: GTPBP1 NM_004286.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71
• Publications: 1 publications found

Genes affected

GTPBP1 (HGNC:4669): (GTP binding protein 1) This gene is upregulated by interferon-gamma and encodes a protein that is a member of the AGP11/GTPBP1 family of GTP-binding proteins. A structurally similar protein has been found in mouse, where disruption of the gene for that protein had no observable phenotype. [provided by RefSeq, Jul 2008]

GTPBP1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1

  Inheritance: AR Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09072697).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004286.5. 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
	GTPBP1	NM_004286.5	MANE Select	c.1153C>T	p.Pro385Ser	missense	Exon 7 of 12	NP_004277.2	O00178

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTPBP1	ENST00000216044.10	TSL:1 MANE Select	c.1153C>T	p.Pro385Ser	missense	Exon 7 of 12	ENSP00000216044.5	O00178
	GTPBP1	ENST00000870601.1		c.1153C>T	p.Pro385Ser	missense	Exon 7 of 13	ENSP00000540660.1
	GTPBP1	ENST00000870603.1		c.1177C>T	p.Pro393Ser	missense	Exon 7 of 12	ENSP00000540662.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000596 AC: 15 AN: 251486 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000814

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461768 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 727198

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.000246 AC: 11 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111902

Other (OTH) AF: 0.0000828 AC: 5 AN: 60388

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152158 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74334

African (AFR) AF: 0.0000241 AC: 1 AN: 41430

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000341 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000576 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.7
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.40	N
REVEL	Benign	0.061
Sift	Benign	0.50	T
Sift4G	Benign	0.44	T
Polyphen		0.0050	B
Vest4		0.12
MutPred		0.53		Gain of phosphorylation at P385 (P = 0.0662)
MVP		0.26
MPC		1.2
ClinPred		0.045	T
GERP RS		4.6
PromoterAI		-0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		0.38
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs750227225; hg19: chr22-39122090; COSMIC: COSV53284284; COSMIC: COSV53284284;