Variant 1-74572464-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001002912.5(ERICH3):c.3246G>T(p.Arg1082Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000352 in 1,613,916 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 2 hom. )

Consequence

ERICH3
NM_001002912.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.110

Variant links:

Genes affected

ERICH3 (HGNC:25346): (glutamate rich 3)

ERICH3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058200598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERICH3	NM_001002912.5 linkuse as main transcript	c.3246G>T	p.Arg1082Ser	missense_variant	14/15	ENST00000326665.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERICH3	ENST00000326665.10 linkuse as main transcript	c.3246G>T	p.Arg1082Ser	missense_variant	14/15	5	NM_001002912.5	P3	Q5RHP9-1
ERICH3	ENST00000433746.2 linkuse as main transcript	n.1388G>T		non_coding_transcript_exon_variant	2/3	1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

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:

0.000456

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000294

AC:

AN:

251322

Hom.:

AF XY:

0.000295

AC XY:

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000867

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:

0.000563

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000365

AC:

533

AN:

1461850

Hom.:

Cov.:

AF XY:

0.000359

AC XY:

261

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000894

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:

0.000451

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000230

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.0000967

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:

0.000456

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000408

Hom.:

Bravo

AF:

0.000242

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000313

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000652

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

Sep 22, 2023

The c.3246G>T (p.R1082S) alteration is located in exon 14 (coding exon 14) of the ERICH3 gene. This alteration results from a G to T substitution at nucleotide position 3246, causing the arginine (R) at amino acid position 1082 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

0.25

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.62

Cadd

Benign

9.3

Dann

Benign

0.92

DEOGEN2

Benign

0.023

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.51

M_CAP

Benign

0.0078

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PROVEAN

Benign

-1.3

REVEL

Benign

0.065

Sift

Benign

0.39

Sift4G

Benign

0.26

Polyphen

0.76

Vest4

0.24

MutPred

0.25

Loss of helix (P = 0.0093);

MVP

0.061

MPC

0.066

ClinPred

0.040

GERP RS

-0.76

Varity_R

0.078

gMVP

0.048

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.

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