Genetic Variant NM_001278182.2:c.1468G>C (chr3-27717720-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001278182.2(EOMES):c.1468G>C(p.Gly490Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G490S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

EOMES
NM_001278182.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

Publications

0 publications found

Variant links:

Genes affected

EOMES (HGNC:3372): (eomesodermin) This gene belongs to the TBR1 (T-box brain protein 1) sub-family of T-box genes that share the common DNA-binding T-box domain. The encoded protein is a transcription factor which is crucial for embryonic development of mesoderm and the central nervous system in vertebrates. The protein may also be necessary for the differentiation of effector CD8+ T cells which are involved in defense against viral infections. A similar gene disrupted in mice is shown to be essential during trophoblast development and gastrulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

EOMES Gene-Disease associations (from GenCC):

microcephaly-polymicrogyria-corpus callosum agenesis syndrome
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet

EOMES links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.25104302).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EOMES	NM_001278182.2 link	c.1468G>C	p.Gly490Arg	missense_variant	Exon 6 of 6	ENST00000449599.4	NP_001265111.1	O95936-4B7Z4K0
EOMES	NM_005442.4 link	c.1411G>C	p.Gly471Arg	missense_variant	Exon 6 of 6		NP_005433.2	O95936-1B7Z4K0
EOMES	NM_001278183.2 link	c.583G>C	p.Gly195Arg	missense_variant	Exon 6 of 6		NP_001265112.1	O95936-3
EOMES	XM_005265510.5 link	c.1459+9G>C		intron_variant	Intron 6 of 6		XP_005265567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EOMES	ENST00000449599.4 link	c.1468G>C	p.Gly490Arg	missense_variant	Exon 6 of 6	1	NM_001278182.2	ENSP00000388620.1	O95936-4
EOMES	ENST00000295743.8 link	c.1411G>C	p.Gly471Arg	missense_variant	Exon 6 of 6	1		ENSP00000295743.4	O95936-1
EOMES	ENST00000461503.2 link	c.583G>C	p.Gly195Arg	missense_variant	Exon 6 of 6	2		ENSP00000487112.1	O95936-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111954

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

T;.;.

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.033

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.45

MutationAssessor

Benign

0.0

N;.;.

PhyloP100

1.7

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.97

N;N;.

REVEL

Uncertain

0.38

Sift

Uncertain

0.0060

D;D;.

Sift4G

Benign

0.11

T;T;T

Polyphen

0.95

P;.;.

Vest4

0.12

MutPred

0.48

Gain of solvent accessibility (P = 0.019);.;.;

MVP

0.73

MPC

1.1

ClinPred

0.62

GERP RS

5.1

Varity_R

0.22

gMVP

0.75

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over