12-104304035-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001008394.3(EID3):ā€‹c.101A>Gā€‹(p.Glu34Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,612,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000085 ( 0 hom., cov: 33)
Exomes š‘“: 0.000016 ( 0 hom. )

Consequence

EID3
NM_001008394.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13875514).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EID3NM_001008394.3 linkuse as main transcriptc.101A>G p.Glu34Gly missense_variant 1/1 ENST00000527879.2
TXNRD1NM_001093771.3 linkuse as main transcriptc.415-7255A>G intron_variant ENST00000525566.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EID3ENST00000527879.2 linkuse as main transcriptc.101A>G p.Glu34Gly missense_variant 1/1 NM_001008394.3 P1
TXNRD1ENST00000525566.6 linkuse as main transcriptc.415-7255A>G intron_variant 1 NM_001093771.3 P1Q16881-1

Frequencies

GnomAD3 genomes
AF:
0.0000855
AC:
13
AN:
152062
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000314
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
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
248272
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134930
show subpopulations
Gnomad AFR exome
AF:
0.0000650
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.0000164
AC:
24
AN:
1459902
Hom.:
0
Cov.:
30
AF XY:
0.0000165
AC XY:
12
AN XY:
726280
show subpopulations
Gnomad4 AFR exome
AF:
0.000358
Gnomad4 AMR exome
AF:
0.0000895
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000829
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152180
Hom.:
0
Cov.:
33
AF XY:
0.0000806
AC XY:
6
AN XY:
74408
show subpopulations
Gnomad4 AFR
AF:
0.000313
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
Alfa
AF:
0.000194
Hom.:
0
Bravo
AF:
0.000189
ExAC
AF:
0.00000826
AC:
1
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 30, 2023The c.101A>G (p.E34G) alteration is located in exon 1 (coding exon 1) of the EID3 gene. This alteration results from a A to G substitution at nucleotide position 101, causing the glutamic acid (E) at amino acid position 34 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.022
T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.50
N
LIST_S2
Benign
0.25
T
M_CAP
Benign
0.0094
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.092
Sift
Benign
0.044
D
Sift4G
Benign
0.13
T
Polyphen
0.82
P
Vest4
0.29
MVP
0.42
MPC
0.39
ClinPred
0.13
T
GERP RS
3.7
Varity_R
0.060
gMVP
0.095

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs569989897; hg19: chr12-104697813; API