Variant 1-27872578-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001105556.3(THEMIS2):c.7C>T(p.Pro3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000224 in 1,337,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P3L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

THEMIS2
NM_001105556.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.399

Variant links:

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]

THEMIS2 links:

THEMIS2 (HGNC:):

THEMIS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09475377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THEMIS2	NM_001105556.3 linkuse as main transcript	c.7C>T	p.Pro3Ser	missense_variant	1/6	ENST00000373921.8	NP_001099026.1	Q5TEJ8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THEMIS2	ENST00000373921.8 linkuse as main transcript	c.7C>T	p.Pro3Ser	missense_variant	1/6	5	NM_001105556.3	ENSP00000363031.3		Q5TEJ8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

91062

Hom.:

AF XY:

0.0000193

AC XY:

AN XY:

51682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000548

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000224

AC:

AN:

1337022

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

660092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000190

Gnomad4 OTH exome

AF:

0.0000181

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.7C>T (p.P3S) alteration is located in exon 1 (coding exon 1) of the THEMIS2 gene. This alteration results from a C to T substitution at nucleotide position 7, causing the proline (P) at amino acid position 3 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.072

.;.;.;.;T;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.82

T;T;T;T;T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.095

T;T;T;T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

2.0

M;M;M;.;.;M

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.6

D;D;D;D;D;N

REVEL

Benign

0.044

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Benign

0.15

T;D;D;D;D;T

Polyphen

0.29

B;D;P;.;.;D

Vest4

0.12

MutPred

0.30

Loss of catalytic residue at P3 (P = 0.0247);Loss of catalytic residue at P3 (P = 0.0247);Loss of catalytic residue at P3 (P = 0.0247);Loss of catalytic residue at P3 (P = 0.0247);Loss of catalytic residue at P3 (P = 0.0247);Loss of catalytic residue at P3 (P = 0.0247);

MVP

0.22

MPC

0.41

ClinPred

0.31

GERP RS

3.0

Varity_R

0.17

gMVP

0.30

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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