Genetic Variant GTPBP10:p.Glu307Ala (chr7-90384910-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033107.4(GTPBP10):c.920A>C(p.Glu307Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GTPBP10
NM_033107.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45

Publications

0 publications found

Variant links:

Genes affected

GTPBP10 (HGNC:25106): (GTP binding protein 10) Small G proteins, such as GTPBP10, act as molecular switches that play crucial roles in the regulation of fundamental cellular processes such as protein synthesis, nuclear transport, membrane trafficking, and signal transduction (Hirano et al., 2006 [PubMed 17054726]).[supplied by OMIM, Mar 2008]

GTPBP10 links:

CLDN12 (HGNC:2034): (claudin 12) This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. This gene is expressed in the inner ear and bladder epithelium, and it is over-expressed in colorectal carcinomas. This protein and claudin 2 are critical for vitamin D-dependent Ca2+ absorption between enterocytes. Multiple alternatively spliced transcript variants encoding the same protein have been found.[provided by RefSeq, Sep 2011]

CLDN12 links:

ENSG00000309151 (HGNC:):

ENSG00000309151 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06966531).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033107.4. 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
	GTPBP10	NM_033107.4	MANE Select	c.920A>C	p.Glu307Ala	missense	Exon 10 of 10	NP_149098.2	A4D1E9-1
	GTPBP10	NM_001042717.3		c.683A>C	p.Glu228Ala	missense	Exon 8 of 8	NP_001036182.1	A4D1E9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GTPBP10	ENST00000222511.11	TSL:1 MANE Select	c.920A>C	p.Glu307Ala	missense	Exon 10 of 10	ENSP00000222511.7	A4D1E9-1
GTPBP10	ENST00000257659.12	TSL:1	c.683A>C	p.Glu228Ala	missense	Exon 8 of 8	ENSP00000257659.8	A4D1E9-2
GTPBP10	ENST00000380058.7	TSL:1	n.*424A>C		non_coding_transcript_exon	Exon 9 of 9	ENSP00000369398.3	A4D1E9-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.0074

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.49

M_CAP

Benign

0.0060

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.78

PhyloP100

1.5

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.7

REVEL

Benign

0.062

Sift

Benign

0.39

Sift4G

Benign

0.37

Polyphen

0.0010

Vest4

0.090

MutPred

0.53

Loss of solvent accessibility (P = 0.0703)

MVP

0.072

MPC

0.030

ClinPred

0.019

GERP RS

-0.97

Varity_R

0.044

gMVP

0.33

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over