Variant 19-4292702-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 ENST00000595645.6(TMIGD2):c.734G>A(p.Ser245Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000624 in 1,603,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

TMIGD2
ENST00000595645.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.627

Variant links:

Genes affected

TMIGD2 (HGNC:28324): (transmembrane and immunoglobulin domain containing 2) Enables coreceptor activity. Involved in positive regulation of T cell activation; positive regulation of angiogenesis; and positive regulation of cytokine production. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

TMIGD2 links:

TMIGD2 (HGNC:):

TMIGD2 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=0.07916638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMIGD2	NM_001169126.2 linkuse as main transcript	c.734G>A	p.Ser245Asn	missense_variant	5/5	ENST00000595645.6	NP_001162597.1	Q96BF3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMIGD2	ENST00000595645.6 linkuse as main transcript	c.734G>A	p.Ser245Asn	missense_variant	5/5	1	NM_001169126.2	ENSP00000470561.1	Q96BF3-2
TMIGD2	ENST00000301272.6 linkuse as main transcript	c.746G>A	p.Ser249Asn	missense_variant	5/5	1		ENSP00000301272.1	Q96BF3-1
TMIGD2	ENST00000600114.5 linkuse as main transcript	c.386G>A	p.Ser129Asn	missense_variant	4/4	1		ENSP00000470494.1	A0A0B4J2A9
TMIGD2	ENST00000600349.1 linkuse as main transcript	c.230G>A	p.Ser77Asn	missense_variant	2/2	1		ENSP00000471821.1	A0A0B4J2B0

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000208

AC:

AN:

240222

Hom.:

AF XY:

0.0000306

AC XY:

AN XY:

130856

show subpopulations

Gnomad AFR exome

AF:

0.000326

Gnomad AMR exome

AF:

0.00

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:

0.00000276

AC:

AN:

1451630

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722026

show subpopulations

Gnomad4 AFR exome

AF:

0.0000915

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:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151998

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

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

Apr 17, 2023

The c.746G>A (p.S249N) alteration is located in exon 5 (coding exon 5) of the TMIGD2 gene. This alteration results from a G to A substitution at nucleotide position 746, causing the serine (S) at amino acid position 249 to be replaced by an asparagine (N). 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

0.19

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.9

DANN

Benign

0.96

DEOGEN2

Benign

0.0066

.;T;T;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.36

T;T;T;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.079

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

.;N;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.3

.;N;.;.

REVEL

Benign

0.075

Sift

Benign

0.17

.;T;.;.

Sift4G

Benign

0.58

T;T;T;T

Polyphen

0.83

P;P;.;.

Vest4

0.15

MVP

0.50

MPC

0.19

ClinPred

0.035

GERP RS

2.2

Varity_R

0.048

gMVP

0.094

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