chr3-27721936-G-GCGGCGGCTGCGC

Position:

• chr3-27721936-G-GCGGCGGCTGCGC

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

The NM_001278182.2(EOMES):​c.358_359insGCGCAGCCGCCG​(p.Ala119_Ala120insGlyAlaAlaAla) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 151,026 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)
• Consequence: EOMES NM_001278182.2 inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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/exons	MANE	UniProt
EOMES	NM_001278182.2	c.358_359insGCGCAGCCGCCG	p.Ala119_Ala120insGlyAlaAlaAla	inframe_insertion	1/6	ENST00000449599.4
EOMES	NM_005442.4	c.358_359insGCGCAGCCGCCG	p.Ala119_Ala120insGlyAlaAlaAla	inframe_insertion	1/6
EOMES	XM_005265510.5	c.358_359insGCGCAGCCGCCG	p.Ala119_Ala120insGlyAlaAlaAla	inframe_insertion	1/7
EOMES	NM_001278183.2	c.-5+493_-5+494insGCGCAGCCGCCG		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EOMES	ENST00000449599.4	c.358_359insGCGCAGCCGCCG	p.Ala119_Ala120insGlyAlaAlaAla	inframe_insertion	1/6	1	NM_001278182.2	A1
EOMES	ENST00000295743.8	c.358_359insGCGCAGCCGCCG	p.Ala119_Ala120insGlyAlaAlaAla	inframe_insertion	1/6	1		P4
EOMES	ENST00000461503.2	c.-5+493_-5+494insGCGCAGCCGCCG		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 151026 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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 Cov.: 35

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 151026 Hom.: 0 Cov.: 0 AF XY: 0.0000136 AC XY: 1 AN XY: 73682

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1553745484; hg19: chr3-27763427;