1-27879782-C-T

Variant names:

• chr1-27879782-C-T
• NM_001105556.3:c.374C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001105556.3(THEMIS2):​c.374C>T​(p.Thr125Ile) variant causes a missense 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: THEMIS2 NM_001105556.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.88
• Publications: 0 publications found

Genes affected

THEMIS2 (HGNC:16839): (thymocyte selection associated family member 2) Predicted to be involved in T cell receptor signaling pathway and regulation of B cell activation. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.14591798).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105556.3. 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
	THEMIS2	NM_001105556.3	MANE Select	c.374C>T	p.Thr125Ile	missense	Exon 3 of 6	NP_001099026.1	Q5TEJ8-1
	THEMIS2	NM_001286113.2		c.374C>T	p.Thr125Ile	missense	Exon 3 of 7	NP_001273042.1	Q5TEJ8-5
	THEMIS2	NM_001286115.2		c.374C>T	p.Thr125Ile	missense	Exon 3 of 6	NP_001273044.1	Q5TEJ8-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THEMIS2	ENST00000373921.8	TSL:5 MANE Select	c.374C>T	p.Thr125Ile	missense	Exon 3 of 6	ENSP00000363031.3	Q5TEJ8-1
	THEMIS2	ENST00000456990.1	TSL:1	c.50C>T	p.Thr17Ile	missense	Exon 1 of 5	ENSP00000398049.1	H7C124
	THEMIS2	ENST00000373925.5	TSL:1	c.374C>T	p.Thr125Ile	missense	Exon 3 of 5	ENSP00000363035.1	Q5TEJ8-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.041
Eigen_PC	Benign	-0.023
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.9
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.026
Sift	Benign	0.10	T
Sift4G	Benign	0.11	T
Polyphen		0.36	B
Vest4		0.27
MutPred		0.30		Gain of catalytic residue at L130 (P = 0.0538)
MVP		0.22
MPC		0.99
ClinPred		0.51	D
GERP RS		3.9
PromoterAI		0.013	Neutral
Varity_R		0.059
gMVP		0.39
Mutation Taster		=90/10	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

hg19: chr1-28206293;