NM_001008394.3:c.347_348delAGinsTC

Variant names:

• chr12-104304281-AG-TC
• NM_001008394.3:c.347_348delAGinsTC
• EID3 p.Gln116Leu

Variant summary

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

The NM_001008394.3(EID3):​c.347_348delAGinsTC​(p.Gln116Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. Q116R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EID3 NM_001008394.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.936
• Publications: 0 publications found

Genes affected

EID3 (HGNC:32961): (EP300 interacting inhibitor of differentiation 3) Predicted to be involved in DNA repair. Located in nucleolus and nucleoplasm. Part of Smc5-Smc6 complex. [provided by Alliance of Genome Resources, Apr 2022]

TXNRD1 (HGNC:12437): (thioredoxin reductase 1) The protein encoded by this gene belongs to the pyridine nucleotide-disulfide oxidoreductase family, and is a member of the thioredoxin (Trx) system. Three thioredoxin reductase (TrxR) isozymes are found in mammals. TrxRs are selenocysteine-containing flavoenzymes, which reduce thioredoxins, as well as other substrates, and play a key role in redox homoeostasis. This gene encodes an ubiquitously expressed, cytosolic form of TrxR, which functions as a homodimer containing FAD, and selenocysteine (Sec) at the active site. Sec is encoded by UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternative splicing, primarily at the 5' end, results in transcript variants encoding same or different isoforms, including a glutaredoxin-containing isoform that is predominantly expressed in testis. [provided by RefSeq, May 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008394.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EID3	NM_001008394.3	MANE Select	c.347_348delAGinsTC	p.Gln116Leu	missense	N/A	NP_001008395.1	Q8N140
	TXNRD1	NM_001093771.3	MANE Select	c.415-7009_415-7008delAGinsTC		intron	N/A	NP_001087240.1	Q16881-1
	TXNRD1	NM_003330.4		c.121-7009_121-7008delAGinsTC		intron	N/A	NP_003321.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EID3	ENST00000527879.2	TSL:6 MANE Select	c.347_348delAGinsTC	p.Gln116Leu	missense	N/A	ENSP00000435619.1	Q8N140
	TXNRD1	ENST00000525566.6	TSL:1 MANE Select	c.415-7009_415-7008delAGinsTC		intron	N/A	ENSP00000434516.1	Q16881-1
	TXNRD1	ENST00000526691.5	TSL:1	c.121-7009_121-7008delAGinsTC		intron	N/A	ENSP00000435929.1	Q16881-4

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.94

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-104698059;