Variant 1-27879739-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001105556.3(THEMIS2):c.331T>C(p.Phe111Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00959 in 1,614,074 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0073 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0098 ( 91 hom. )

Consequence

THEMIS2
NM_001105556.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.83

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005374044).

BP6

Variant 1-27879739-T-C is Benign according to our data. Variant chr1-27879739-T-C is described in ClinVar as [Benign]. Clinvar id is 777747.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THEMIS2	NM_001105556.3 linkuse as main transcript	c.331T>C	p.Phe111Leu	missense_variant	3/6	ENST00000373921.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THEMIS2	ENST00000373921.8 linkuse as main transcript	c.331T>C	p.Phe111Leu	missense_variant	3/6	5	NM_001105556.3	P1	Q5TEJ8-1

Frequencies

GnomAD3 genomes

AF:

0.00734

AC:

1116

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00701

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00840

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00819

AC:

2059

AN:

251432

Hom.:

AF XY:

0.00789

AC XY:

1072

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00546

Gnomad ASJ exome

AF:

0.0141

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00183

Gnomad FIN exome

AF:

0.00961

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.00864

GnomAD4 exome

AF:

0.00982

AC:

14356

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00961

AC XY:

6988

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00185

Gnomad4 AMR exome

AF:

0.00613

Gnomad4 ASJ exome

AF:

0.0154

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00176

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.0112

Gnomad4 OTH exome

AF:

0.00795

GnomAD4 genome

AF:

0.00733

AC:

1116

AN:

152198

Hom.:

Cov.:

AF XY:

0.00710

AC XY:

528

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00700

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00840

Gnomad4 NFE

AF:

0.0114

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.00728

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0141

AC:

121

ExAC

AF:

0.00833

AC:

1011

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0101

EpiControl

AF:

0.0116

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.055

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.75

T;T;T;T

MetaRNN

Benign

0.0054

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Pathogenic

3.0

M;M;.;M

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.6

D;D;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.048

D;T;T;D

Polyphen

0.87

P;D;.;P

Vest4

0.76

MutPred

0.53

Gain of catalytic residue at F111 (P = 0.0761);Gain of catalytic residue at F111 (P = 0.0761);.;Gain of catalytic residue at F111 (P = 0.0761);

MVP

0.19

MPC

0.93

ClinPred

0.060

GERP RS

3.5

Varity_R

0.48

gMVP

0.77

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

Other links and lift over