GeneBe

3-27721936-G-GCGGAGC

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_001278182.2(EOMES):​c.358_359insGCTCCG​(p.Ala119_Ala120insGlySer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,364,148 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A120A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 0)
Exomes 𝑓: 8.2e-7 ( 0 hom. )

Consequence

EOMES
NM_001278182.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.62

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_001278182.2

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EOMESNM_001278182.2 linkc.358_359insGCTCCG p.Ala119_Ala120insGlySer conservative_inframe_insertion Exon 1 of 6 ENST00000449599.4 NP_001265111.1 O95936-4B7Z4K0
EOMESNM_005442.4 linkc.358_359insGCTCCG p.Ala119_Ala120insGlySer conservative_inframe_insertion Exon 1 of 6 NP_005433.2 O95936-1B7Z4K0
EOMESXM_005265510.5 linkc.358_359insGCTCCG p.Ala119_Ala120insGlySer conservative_inframe_insertion Exon 1 of 7 XP_005265567.1
EOMESNM_001278183.2 linkc.-5+493_-5+494insGCTCCG intron_variant Intron 1 of 5 NP_001265112.1 O95936-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EOMESENST00000449599.4 linkc.358_359insGCTCCG p.Ala119_Ala120insGlySer conservative_inframe_insertion Exon 1 of 6 1 NM_001278182.2 ENSP00000388620.1 O95936-4
EOMESENST00000295743.8 linkc.358_359insGCTCCG p.Ala119_Ala120insGlySer conservative_inframe_insertion Exon 1 of 6 1 ENSP00000295743.4 O95936-1
EOMESENST00000461503.2 linkc.-5+493_-5+494insGCTCCG intron_variant Intron 1 of 5 2 ENSP00000487112.1 O95936-3

Frequencies

GnomAD3 genomes
AF:
0.00000662
AC:
1
AN:
151026
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000660
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
GnomAD4 exome
AF:
8.24e-7
AC:
1
AN:
1213122
Hom.:
0
Cov.:
35
AF XY:
0.00000169
AC XY:
1
AN XY:
591022
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
23740
American (AMR)
AF:
0.00
AC:
0
AN:
9520
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
17262
East Asian (EAS)
AF:
0.00
AC:
0
AN:
26210
South Asian (SAS)
AF:
0.0000230
AC:
1
AN:
43446
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
41800
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3352
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
998342
Other (OTH)
AF:
0.00
AC:
0
AN:
49450
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.00000662
AC:
1
AN:
151026
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
73682
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41210
American (AMR)
AF:
0.0000660
AC:
1
AN:
15158
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3460
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4990
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4804
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10432
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
306
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67684
Other (OTH)
AF:
0.00
AC:
0
AN:
2076
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.675
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
310

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.6
Mutation Taster
=86/14
polymorphism

Splicing

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

Publications

Other links and lift over

dbSNP: rs1553745484; hg19: chr3-27763427; API