1-44339314-C-A

Position:

• chr1-44339314-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024066.3(ERI3):​c.220G>T​(p.Ala74Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000054 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ERI3 NM_024066.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41531846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERI3	NM_024066.3	c.220G>T	p.Ala74Ser	missense_variant	3/9	ENST00000372257.7	NP_076971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERI3	ENST00000372257.7	c.220G>T	p.Ala74Ser	missense_variant	3/9	1	NM_024066.3	ENSP00000361331.2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000539 AC: 6 AN: 1112506 Hom.: 0 Cov.: 36 AF XY: 0.00000554 AC XY: 3 AN XY: 541782

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000359

Gnomad4 SAS exome AF: 0.0000236

Gnomad4 FIN exome AF: 0.0000240

Gnomad4 NFE exome AF: 0.00000226

Gnomad4 OTH exome AF: 0.0000228

GnomAD4 genome Cov.: 28

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 12, 2023

The c.220G>T (p.A74S) alteration is located in exon 3 (coding exon 3) of the ERI3 gene. This alteration results from a G to T substitution at nucleotide position 220, causing the alanine (A) at amino acid position 74 to be replaced by a serine (S). 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	0.089
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T;.;.
Eigen	Benign	0.076
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D;D;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.15	N;.;N
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D;.;D
Sift4G	Pathogenic	0.0	D;.;.
Polyphen		0.24	B;.;P
Vest4		0.31
MutPred		0.75		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);.;
MVP		0.34
MPC		0.70
ClinPred		0.59	D
GERP RS		4.0
Varity_R		0.31
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-44804986;