rs371113667

Variant names:

• chr3-27717645-C-A
• rs371113667
• NM_001278182.2:c.1543G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-27717645-C-A
• chr3-27717645-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001278182.2(EOMES):​c.1543G>T​(p.Val515Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V515M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EOMES NM_001278182.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.50
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EOMES	NM_001278182.2	c.1543G>T	p.Val515Leu	missense_variant	Exon 6 of 6	ENST00000449599.4	NP_001265111.1
EOMES	NM_005442.4	c.1486G>T	p.Val496Leu	missense_variant	Exon 6 of 6		NP_005433.2
EOMES	NM_001278183.2	c.658G>T	p.Val220Leu	missense_variant	Exon 6 of 6		NP_001265112.1
EOMES	XM_005265510.5	c.1460-36G>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.1543G>T	p.Val515Leu	missense_variant	Exon 6 of 6	1	NM_001278182.2	ENSP00000388620.1
EOMES	ENST00000295743.8	c.1486G>T	p.Val496Leu	missense_variant	Exon 6 of 6	1		ENSP00000295743.4
EOMES	ENST00000461503.2	c.658G>T	p.Val220Leu	missense_variant	Exon 6 of 6	2		ENSP00000487112.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;.;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Uncertain	0.096	D
MutationAssessor	Uncertain	2.3	M;.;.
PhyloP100		7.5
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.90	N;N;.
REVEL	Uncertain	0.50
Sift	Benign	0.046	D;T;.
Sift4G	Benign	0.18	T;T;T
Polyphen		0.95	P;.;.
Vest4		0.61
MutPred		0.19		Loss of phosphorylation at T499 (P = 0.1777);.;.;
MVP		0.90
MPC		1.6
ClinPred		0.95	D
GERP RS		4.7
Varity_R		0.22
gMVP		0.50
Mutation Taster		=35/65	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs371113667; hg19: chr3-27759136;