6-127850874-A-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010923.3(THEMIS):​c.250+4156T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 151,742 control chromosomes in the GnomAD database, including 669 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 0.033 (669 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THEMIS	NM_001010923.3	c.250+4156T>G		intron_variant	Intron 2 of 5	ENST00000368248.5	NP_001010923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THEMIS	ENST00000368248.5	c.250+4156T>G		intron_variant	Intron 2 of 5	1	NM_001010923.3	ENSP00000357231.2

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5011 AN: 151626 Hom.: 663 Cov.: 32

Gnomad AFR AF: 0.00426

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.00606

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00181

Gnomad OTH AF: 0.0369

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

GnomAD4 genome AF: 0.0331 AC: 5027 AN: 151742 Hom.: 669 Cov.: 32 AF XY: 0.0380 AC XY: 2821 AN XY: 74154

African (AFR) AF: 0.00424 AC: 176 AN: 41476

American (AMR) AF: 0.138 AC: 2095 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.00606 AC: 21 AN: 3464

East Asian (EAS) AF: 0.407 AC: 2080 AN: 5112

South Asian (SAS) AF: 0.0479 AC: 231 AN: 4822

European-Finnish (FIN) AF: 0.0209 AC: 221 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00181 AC: 123 AN: 67786

Other (OTH) AF: 0.0380 AC: 80 AN: 2108

Alfa AF: 0.0166 Hom.: 105

Bravo AF: 0.0444

Asia WGS AF: 0.192 AC: 666 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.45
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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;