chr6-127850874-A-T

Variant names:

• chr6-127850874-A-T
• rs9398855
• NM_001010923.3:c.250+4156T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001010923.3(THEMIS):​c.250+4156T>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: THEMIS NM_001010923.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.358
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010923.3. 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
	THEMIS	NM_001010923.3	MANE Select	c.250+4156T>A		intron	N/A	NP_001010923.1
	THEMIS	NM_001164685.2		c.250+4156T>A		intron	N/A	NP_001158157.1
	THEMIS	NM_001394520.1		c.145+4156T>A		intron	N/A	NP_001381449.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THEMIS	ENST00000368248.5	TSL:1 MANE Select	c.250+4156T>A		intron	N/A	ENSP00000357231.2
	THEMIS	ENST00000630369.2	TSL:1	c.250+4156T>A		intron	N/A	ENSP00000487358.1
	THEMIS	ENST00000852157.1		c.250+4156T>A		intron	N/A	ENSP00000522216.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.35
PhyloP100		0.36

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: rs9398855; hg19: chr6-128172019;