7-90384910-A-G

Variant names:

• chr7-90384910-A-G
• rs778015258
• NM_033107.4:c.920A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033107.4(GTPBP10):​c.920A>G​(p.Glu307Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,434,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E307A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GTPBP10 NM_033107.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 0 publications found

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]

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]

ENSG00000309151 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062051833).

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>G	p.Glu307Gly	missense	Exon 10 of 10	NP_149098.2	A4D1E9-1
	GTPBP10	NM_001042717.3		c.683A>G	p.Glu228Gly	missense	Exon 8 of 8	NP_001036182.1	A4D1E9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTPBP10	ENST00000222511.11	TSL:1 MANE Select	c.920A>G	p.Glu307Gly	missense	Exon 10 of 10	ENSP00000222511.7	A4D1E9-1
	GTPBP10	ENST00000257659.12	TSL:1	c.683A>G	p.Glu228Gly	missense	Exon 8 of 8	ENSP00000257659.8	A4D1E9-2
	GTPBP10	ENST00000380058.7	TSL:1	n.*424A>G		non_coding_transcript_exon	Exon 9 of 9	ENSP00000369398.3	A4D1E9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000437 AC: 1 AN: 228780 AF XY: 0.00000809

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1434560 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 712048

African (AFR) AF: 0.00 AC: 0 AN: 32084

American (AMR) AF: 0.00 AC: 0 AN: 38860

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39102

South Asian (SAS) AF: 0.0000248 AC: 2 AN: 80676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101118

Other (OTH) AF: 0.00 AC: 0 AN: 59202

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Benign	0.82
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.32	N
PhyloP100		1.5
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.060
Sift	Benign	0.32	T
Sift4G	Benign	0.31	T
Polyphen		0.0010	B
Vest4		0.056
MutPred		0.48		Loss of stability (P = 0.0459)
MVP		0.092
MPC		0.032
ClinPred		0.026	T
GERP RS		-0.97
Varity_R		0.039
gMVP		0.35
Mutation Taster		=95/5	polymorphism

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: rs778015258; hg19: chr7-90014224;