Variant 1-74590078-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001002912.5(ERICH3):c.1729A>G(p.Met577Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,427,846 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ERICH3
NM_001002912.5 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.218

Variant links:

Genes affected

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

ERICH3 links:

ERICH3-AS1 (HGNC:41093): (ERICH3 antisense RNA 1)

ERICH3-AS1 links:

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=0.012027115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERICH3	NM_001002912.5 link	c.1729A>G	p.Met577Val	missense_variant, splice_region_variant	12/15	ENST00000326665.10	NP_001002912.4	Q5RHP9-1
ERICH3	XM_017000275.2 link	c.1723A>G	p.Met575Val	missense_variant, splice_region_variant	12/14		XP_016855764.1
ERICH3-AS1	NR_121670.1 link	n.173+171T>C		intron_variant
ERICH3-AS1	NR_121671.1 link	n.80+12569T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERICH3	ENST00000326665.10 link	c.1729A>G	p.Met577Val	missense_variant, splice_region_variant	12/15	5	NM_001002912.5	ENSP00000322609.5		Q5RHP9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

213808

Hom.:

AF XY:

0.0000260

AC XY:

AN XY:

115494

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000373

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000193

GnomAD4 exome

AF:

0.0000105

AC:

AN:

1427846

Hom.:

Cov.:

AF XY:

0.00000848

AC XY:

AN XY:

707208

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000205

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000457

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000248

AC:

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

Oct 09, 2024

The c.1729A>G (p.M577V) alteration is located in exon 12 (coding exon 12) of the ERICH3 gene. This alteration results from a A to G substitution at nucleotide position 1729, causing the methionine (M) at amino acid position 577 to be replaced by a valine (V). 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

0.058

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.79

DANN

Benign

0.69

DEOGEN2

Benign

0.0016

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.38

T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.20

N;.

PROVEAN

Benign

-0.34

N;N

REVEL

Benign

0.022

Sift

Benign

0.67

T;T

Sift4G

Benign

0.81

T;T

Polyphen

0.0020

B;B

Vest4

0.014

MutPred

0.20

Gain of methylation at K578 (P = 0.0169);.;

MVP

0.072

MPC

0.018

ClinPred

0.013

GERP RS

-1.5

Varity_R

0.041

gMVP

0.027

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