chr10-70771387-C-T

Variant names:

• chr10-70771387-C-T
• rs765309690
• NM_001318241.2:c.1048G>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.1048G>A​(p.Ala350Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TBATA NM_001318241.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01
• Publications: 1 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=0.10764393).

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.1048G>A	p.Ala350Thr	missense	Exon 11 of 11	NP_001305170.1	A0A0A0MSR7
	TBATA	NM_001318242.2		c.1045G>A	p.Ala349Thr	missense	Exon 11 of 11	NP_001305171.1	Q96M53-1
	TBATA	NM_152710.4		c.1045G>A	p.Ala349Thr	missense	Exon 11 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.1048G>A	p.Ala350Thr	missense	Exon 11 of 11	ENSP00000400224.3	A0A0A0MSR7
	TBATA	ENST00000299290.5	TSL:1	c.1045G>A	p.Ala349Thr	missense	Exon 11 of 11	ENSP00000299290.1	Q96M53-1
	TBATA	ENST00000692183.1		c.1045G>A	p.Ala349Thr	missense	Exon 11 of 11	ENSP00000509602.1	Q96M53-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251480 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 6.84e-7 AC: 1 AN: 1461870 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727242

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

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

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	0.086
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.7
DANN	Benign	0.89
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.0
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.063
Sift	Benign	0.080	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.073	B
Vest4		0.19
MutPred		0.12		Gain of phosphorylation at A349 (P = 0.0042)
MVP		0.040
MPC		0.095
ClinPred		0.30	T
GERP RS		1.6
Varity_R		0.036
gMVP		0.093
Mutation Taster		=96/4	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: rs765309690; hg19: chr10-72531143;