rs12194062

Positions:

• chr6-127873328-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010923.3(THEMIS):​c.92-18140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 151,996 control chromosomes in the GnomAD database, including 3,790 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3790 hom., cov: 32)
• Consequence: THEMIS NM_001010923.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.781

Genes affected

THEMIS (HGNC:21569): (thymocyte selection associated) This gene encodes a protein that plays a regulatory role in both positive and negative T-cell selection during late thymocyte development. The protein functions through T-cell antigen receptor signaling, and is necessary for proper lineage commitment and maturation of T-cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THEMIS	NM_001010923.3	c.92-18140G>A		intron_variant		ENST00000368248.5	NP_001010923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THEMIS	ENST00000368248.5	c.92-18140G>A		intron_variant		1	NM_001010923.3	ENSP00000357231	P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29632 AN: 151878 Hom.: 3793 Cov.: 32

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.217

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.195 AC: 29626 AN: 151996 Hom.: 3790 Cov.: 32 AF XY: 0.191 AC XY: 14168 AN XY: 74256

Gnomad4 AFR AF: 0.0583

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.214

Alfa AF: 0.270 Hom.: 7628

Bravo AF: 0.183

Asia WGS AF: 0.0670 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.6
DANN	Benign	0.90

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

LitVar

Other links and lift over

dbSNP: rs12194062; hg19: chr6-128194473;