Variant 1-44339223-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024066.3(ERI3):c.311C>T(p.Ser104Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ERI3
NM_024066.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

Variant links:

Genes affected

ERI3 (HGNC:17276): (ERI1 exoribonuclease family member 3) Enables RNA binding activity. Predicted to be involved in exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). [provided by Alliance of Genome Resources, Apr 2022]

ERI3 links:

ERI3 (HGNC:):

ERI3 links:

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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=0.116096705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERI3	NM_024066.3 linkuse as main transcript	c.311C>T	p.Ser104Phe	missense_variant	3/9	ENST00000372257.7	NP_076971.1	O43414-1B4DEX5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERI3	ENST00000372257.7 linkuse as main transcript	c.311C>T	p.Ser104Phe	missense_variant	3/9	1	NM_024066.3	ENSP00000361331.2		O43414-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251142

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.311C>T (p.S104F) alteration is located in exon 3 (coding exon 3) of the ERI3 gene. This alteration results from a C to T substitution at nucleotide position 311, causing the serine (S) at amino acid position 104 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

T;.;.

Eigen

Benign

-0.052

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.0014

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.63

N;.;N

REVEL

Benign

0.044

Sift

Uncertain

0.0010

D;.;D

Sift4G

Uncertain

0.0020

D;.;.

Polyphen

0.0010

B;.;B

Vest4

0.17

MutPred

0.35

Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);.;

MVP

0.39

MPC

0.79

ClinPred

0.22

GERP RS

6.2

Varity_R

0.13

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over