rs9491859

chr6-127743218-A-C

Variant summary

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

The NM_001010923.3(THEMIS):c.1759-23395T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,844 control chromosomes in the GnomAD database, including 26,654 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 0.58 (26654 hom., cov: 30)
• Consequence: THEMIS NM_001010923.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THEMIS	NM_001010923.3	c.1759-23395T>G		intron_variant		ENST00000368248.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THEMIS	ENST00000368248.5	c.1759-23395T>G		intron_variant		1	NM_001010923.3	P1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87534 AN: 151722 Hom.: 26619 Cov.: 30

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.0732

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.577 AC: 87621 AN: 151844 Hom.: 26654 Cov.: 30 AF XY: 0.564 AC XY: 41833 AN XY: 74218

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.0735

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.534

Alfa AF: 0.619 Hom.: 47107

Bravo AF: 0.563

Asia WGS AF: 0.221 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	2.8
Dann	Benign	0.37

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: rs9491859; hg19: chr6-128064363;