10-70777301-C-T

Variant names:

• chr10-70777301-C-T
• rs376611245
• NM_001318241.2:c.545G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318241.2(TBATA):​c.545G>A​(p.Gly182Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: TBATA NM_001318241.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41
• Publications: 0 publications found

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]

ACMG classification

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=0.20470235).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318241.2. 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
	TBATA	NM_001318241.2	MANE Select	c.545G>A	p.Gly182Glu	missense	Exon 7 of 11	NP_001305170.1	A0A0A0MSR7
	TBATA	NM_001318242.2		c.542G>A	p.Gly181Glu	missense	Exon 7 of 11	NP_001305171.1	Q96M53-1
	TBATA	NM_152710.4		c.542G>A	p.Gly181Glu	missense	Exon 7 of 11	NP_689923.3	Q96M53-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBATA	ENST00000456372.4	TSL:1 MANE Select	c.545G>A	p.Gly182Glu	missense	Exon 7 of 11	ENSP00000400224.3	A0A0A0MSR7
	TBATA	ENST00000299290.5	TSL:1	c.542G>A	p.Gly181Glu	missense	Exon 7 of 11	ENSP00000299290.1	Q96M53-1
	TBATA	ENST00000692183.1		c.542G>A	p.Gly181Glu	missense	Exon 7 of 11	ENSP00000509602.1	Q96M53-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 250844 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

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: 0.00000684 AC: 10 AN: 1461434 Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5 AN XY: 727064

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

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

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111900

Other (OTH) AF: 0.0000497 AC: 3 AN: 60386

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74298

African (AFR) AF: 0.0000241 AC: 1 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.00115 AC: 4 AN: 3478

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	0.24
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.080	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.061
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.4
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.055
Sift	Benign	0.085	T
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.44
MutPred		0.20		Gain of helix (P = 0.0082)
MVP		0.16
MPC		0.54
ClinPred		0.63	D
GERP RS		3.1
Varity_R		0.091
gMVP		0.12
Mutation Taster		=100/0	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: rs376611245; hg19: chr10-72537057; COSMIC: COSV54719845; COSMIC: COSV54719845;