NM_001278182.2:c.1176C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001278182.2(EOMES):c.1176C>T(p.Ser392Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000565 in 1,612,780 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 2 hom. )

Consequence

EOMES
NM_001278182.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.20

Publications

2 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: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 3-27718876-G-A is Benign according to our data. Variant chr3-27718876-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 771851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.2 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EOMES	NM_001278182.2 link	c.1176C>T	p.Ser392Ser	synonymous_variant	Exon 4 of 6	ENST00000449599.4	NP_001265111.1	O95936-4B7Z4K0
EOMES	NM_005442.4 link	c.1176C>T	p.Ser392Ser	synonymous_variant	Exon 4 of 6		NP_005433.2	O95936-1B7Z4K0
EOMES	NM_001278183.2 link	c.291C>T	p.Ser97Ser	synonymous_variant	Exon 4 of 6		NP_001265112.1	O95936-3
EOMES	XM_005265510.5 link	c.1176C>T	p.Ser392Ser	synonymous_variant	Exon 4 of 7		XP_005265567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EOMES	ENST00000449599.4 link	c.1176C>T	p.Ser392Ser	synonymous_variant	Exon 4 of 6	1	NM_001278182.2	ENSP00000388620.1	O95936-4
EOMES	ENST00000295743.8 link	c.1176C>T	p.Ser392Ser	synonymous_variant	Exon 4 of 6	1		ENSP00000295743.4	O95936-1
EOMES	ENST00000461503.2 link	c.291C>T	p.Ser97Ser	synonymous_variant	Exon 4 of 6	2		ENSP00000487112.1	O95936-3

Frequencies

GnomAD3 genomes

AF:

0.000644

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000741

AC:

186

AN:

250992

AF XY:

0.000870

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000828

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.000557

AC:

813

AN:

1460536

Hom.:

Cov.:

AF XY:

0.000633

AC XY:

460

AN XY:

726414

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33444

American (AMR)

AF:

0.000918

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00103

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.000859

AC:

AN:

86182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.0118

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000476

AC:

529

AN:

1110984

Other (OTH)

AF:

0.000961

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

119

159

199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000644

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41536

American (AMR)

AF:

0.00177

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00145

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000809

AC:

AN:

68014

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00102

Hom.:

Bravo

AF:

0.000884

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

EOMES: BP4, BP7 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 01, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.8

(source)

DANN

Benign

0.78

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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NM_001278182.2:c.1176C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over