3-27718876-G-C

Variant names:

• chr3-27718876-G-C
• rs147676215
• NM_001278182.2:c.1176C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001278182.2(EOMES):​c.1176C>G​(p.Ser392Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,542 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. Synonymous variant affecting the same amino acid position (i.e. S392S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: EOMES NM_001278182.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 2 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=2.2 with no splicing effect.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 250992 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460542 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726418

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.0000671 AC: 3 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110986

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.8
DANN	Benign	0.76
PhyloP100		2.2

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: rs147676215; hg19: chr3-27760367;