NM_001278182.2:c.1487C>T

Variant names:

• chr3-27717701-G-A
• rs137915789
• NM_001278182.2:c.1487C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001278182.2(EOMES):​c.1487C>T​(p.Pro496Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,613,854 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. P496R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: EOMES NM_001278182.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.39
• Publications: 4 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17663765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EOMES	NM_001278182.2	c.1487C>T	p.Pro496Leu	missense_variant	Exon 6 of 6	ENST00000449599.4	NP_001265111.1
EOMES	NM_005442.4	c.1430C>T	p.Pro477Leu	missense_variant	Exon 6 of 6		NP_005433.2
EOMES	NM_001278183.2	c.602C>T	p.Pro201Leu	missense_variant	Exon 6 of 6		NP_001265112.1
EOMES	XM_005265510.5	c.1459+28C>T		intron_variant	Intron 6 of 6		XP_005265567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EOMES	ENST00000449599.4	c.1487C>T	p.Pro496Leu	missense_variant	Exon 6 of 6	1	NM_001278182.2	ENSP00000388620.1
EOMES	ENST00000295743.8	c.1430C>T	p.Pro477Leu	missense_variant	Exon 6 of 6	1		ENSP00000295743.4
EOMES	ENST00000461503.2	c.602C>T	p.Pro201Leu	missense_variant	Exon 6 of 6	2		ENSP00000487112.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 151970 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000394

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

GnomAD2 exomes AF: 0.0000320 AC: 8 AN: 250052 AF XY: 0.0000296

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000150 AC: 22 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 727246

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1112002

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 151970 Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7 AN XY: 74206

African (AFR) AF: 0.0000725 AC: 3 AN: 41368

American (AMR) AF: 0.000394 AC: 6 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000147 Hom.: 0

Bravo AF: 0.0000302

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000412 AC: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.74	D;.;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	0.81	L;.;.
PhyloP100		5.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.1	D;D;.
REVEL	Uncertain	0.35
Sift	Benign	0.11	T;T;.
Sift4G	Benign	0.26	T;T;D
Polyphen		0.95	P;.;.
Vest4		0.22
MVP		0.66
MPC		0.89
ClinPred		0.079	T
GERP RS		4.2
Varity_R		0.15
gMVP		0.34
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs137915789; hg19: chr3-27759192; COSMIC: COSV55414243; COSMIC: COSV55414243;