NM_001002912.5:c.3892G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001002912.5(ERICH3):​c.3892G>A​(p.Glu1298Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ERICH3
NM_001002912.5 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.334
Variant links:
Genes affected
ERICH3 (HGNC:25346): (glutamate rich 3)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.029308587).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ERICH3NM_001002912.5 linkc.3892G>A p.Glu1298Lys missense_variant Exon 14 of 15 ENST00000326665.10 NP_001002912.4 Q5RHP9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ERICH3ENST00000326665.10 linkc.3892G>A p.Glu1298Lys missense_variant Exon 14 of 15 5 NM_001002912.5 ENSP00000322609.5 Q5RHP9-1
ERICH3ENST00000433746.2 linkn.2034G>A non_coding_transcript_exon_variant Exon 2 of 3 1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000359
AC:
9
AN:
250576
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135506
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1461036
Hom.:
0
Cov.:
87
AF XY:
0.0000275
AC XY:
20
AN XY:
726910
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000278
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152324
Hom.:
0
Cov.:
32
AF XY:
0.0000268
AC XY:
2
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3892G>A (p.E1298K) alteration is located in exon 14 (coding exon 14) of the ERICH3 gene. This alteration results from a G to A substitution at nucleotide position 3892, causing the glutamic acid (E) at amino acid position 1298 to be replaced by a lysine (K). 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
0.076
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
3.7
DANN
Benign
0.96
DEOGEN2
Benign
0.0086
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.023
N
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.0094
T
MetaRNN
Benign
0.029
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.6
L
PROVEAN
Benign
-0.72
N
REVEL
Benign
0.013
Sift
Benign
0.20
T
Sift4G
Benign
0.20
T
Polyphen
0.021
B
Vest4
0.17
MutPred
0.35
Gain of ubiquitination at E1298 (P = 0.0082);
MVP
0.072
MPC
0.022
ClinPred
0.043
T
GERP RS
-0.48
Varity_R
0.062
gMVP
0.030

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: rs558628317; hg19: chr1-75037502; API