10-70774222-G-C

Position:

• chr10-70774222-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318241.2(TBATA):​c.911C>G​(p.Pro304Arg) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TBATA NM_001318241.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0320

Genes affected

TBATA (HGNC:23511): (thymus, brain and testes associated) This gene encodes a protein that regulates thymic epithelial cell proliferation and thymus size. It has been identified as a ligand for the class I human leukocyte antigen (HLA-I) in thymus. Studies of the orthologous mouse protein suggest that it may also play a role in spermatid differentiation, as well as in neuronal morphogenesis and synaptic plasticity. Polymorphisms in this gene are associated with susceptibility for multiple sclerosis (MS). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

TBATA (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06931636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBATA	NM_001318241.2	c.911C>G	p.Pro304Arg	missense_variant	9/11	ENST00000456372.4	NP_001305170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBATA	ENST00000456372.4	c.911C>G	p.Pro304Arg	missense_variant	9/11	1	NM_001318241.2	ENSP00000400224.3
TBATA	ENST00000692183.1	c.908C>G	p.Pro303Arg	missense_variant	9/11			ENSP00000509602.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.908C>G (p.P303R) alteration is located in exon 9 (coding exon 7) of the TBATA gene. This alteration results from a C to G substitution at nucleotide position 908, causing the proline (P) at amino acid position 303 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.9
DANN	Benign	0.34
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.74	N;.
REVEL	Benign	0.046
Sift	Benign	0.14	T;.
Sift4G	Benign	0.099	T;T
Polyphen		0.63	P;.
Vest4		0.14
MutPred		0.14		Loss of glycosylation at P303 (P = 0.0171);.;
MVP		0.048
MPC		0.22
ClinPred		0.13	T
GERP RS		-1.4
Varity_R		0.031
gMVP		0.047

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-72533978;