Variant 8-98089670-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_173549.3(ERICH5):c.653T>C(p.Leu218Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,613,998 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

ERICH5
NM_173549.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.03

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0121243).

BP6

Variant 8-98089670-T-C is Benign according to our data. Variant chr8-98089670-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2589289.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERICH5	NM_173549.3 linkuse as main transcript	c.653T>C	p.Leu218Pro	missense_variant	2/3	ENST00000318528.8	NP_775820.2
ERICH5	NM_001170806.2 linkuse as main transcript	c.59-3551T>C		intron_variant			NP_001164277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERICH5	ENST00000318528.8 linkuse as main transcript	c.653T>C	p.Leu218Pro	missense_variant	2/3	1	NM_173549.3	ENSP00000315614	P1	Q6P6B1-1
ERICH5	ENST00000545282.1 linkuse as main transcript	c.59-3551T>C		intron_variant		2		ENSP00000440297		Q6P6B1-2

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000108

AC:

AN:

249460

Hom.:

AF XY:

0.0000887

AC XY:

AN XY:

135322

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00160

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000595

AC:

AN:

1461820

Hom.:

Cov.:

AF XY:

0.0000784

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000205

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.000124

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.2

DANN

Benign

0.95

DEOGEN2

Benign

0.028

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0082

LIST_S2

Benign

0.33

M_CAP

Benign

0.0082

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.99

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

0.61

REVEL

Benign

0.018

Sift

Benign

0.15

Sift4G

Benign

0.17

Polyphen

0.016

Vest4

0.079

MutPred

0.25

Loss of stability (P = 0.0332);

MVP

0.081

MPC

0.39

ClinPred

0.030

GERP RS

-4.3

Varity_R

0.063

gMVP

0.029

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