Variant 8-98089695-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_173549.3(ERICH5):c.678A>C(p.Glu226Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,614,186 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 3 hom. )

Consequence

ERICH5
NM_173549.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.438

Variant links:

Genes affected

ERICH5 (HGNC:26823): (glutamate rich 5)

ERICH5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012241334).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERICH5	NM_173549.3 link	c.678A>C	p.Glu226Asp	missense_variant	2/3	ENST00000318528.8	NP_775820.2	Q6P6B1-1
ERICH5	NM_001170806.2 link	c.59-3526A>C		intron_variant			NP_001164277.1	Q6P6B1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERICH5	ENST00000318528.8 link	c.678A>C	p.Glu226Asp	missense_variant	2/3	1	NM_173549.3	ENSP00000315614.3		Q6P6B1-1
ERICH5	ENST00000545282.1 link	c.59-3526A>C		intron_variant		2		ENSP00000440297.1		Q6P6B1-2

Frequencies

GnomAD3 genomes

AF:

0.000637

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000985

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000704

AC:

176

AN:

250050

Hom.:

AF XY:

0.000738

AC XY:

100

AN XY:

135486

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.000797

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.000984

GnomAD4 exome

AF:

0.00106

AC:

1556

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

760

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000600

Gnomad4 NFE exome

AF:

0.00125

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.000637

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.000733

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000651

AC:

EpiCase

AF:

0.00131

EpiControl

AF:

0.00124

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

Jul 09, 2021

The c.678A>C (p.E226D) alteration is located in exon 2 (coding exon 2) of the ERICH5 gene. This alteration results from a A to C substitution at nucleotide position 678, causing the glutamic acid (E) at amino acid position 226 to be replaced by an aspartic acid (D). 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

0.13

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.35

M_CAP

Benign

0.0055

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PROVEAN

Benign

-2.2

REVEL

Benign

0.044

Sift

Benign

0.19

Sift4G

Benign

0.25

Polyphen

0.91

Vest4

0.097

MutPred

0.10

Loss of methylation at K223 (P = 0.0875);

MVP

0.21

MPC

0.25

ClinPred

0.049

GERP RS

2.7

Varity_R

0.079

gMVP

0.018

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