Genetic Variant ERICH6B:p.Glu633Lys (chr13-45541656-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_182542.3(ERICH6B):c.1897G>A(p.Glu633Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000903 in 1,550,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

ERICH6B
NM_182542.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00600

Variant links:

Genes affected

ERICH6B (HGNC:26523): (glutamate rich 6B)

ERICH6B 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=0.027086765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERICH6B	NM_182542.3 link	c.1897G>A	p.Glu633Lys	missense_variant	Exon 15 of 15	ENST00000298738.3	NP_872348.2	Q5W0A0-1
ERICH6B	XM_011534965.3 link	c.1969G>A	p.Glu657Lys	missense_variant	Exon 14 of 14		XP_011533267.1
ERICH6B	XM_017020418.2 link	c.1897G>A	p.Glu633Lys	missense_variant	Exon 14 of 14		XP_016875907.1	Q5W0A0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERICH6B	ENST00000298738.3 link	c.1897G>A	p.Glu633Lys	missense_variant	Exon 15 of 15	2	NM_182542.3	ENSP00000298738.2		Q5W0A0-1
ERICH6B	ENST00000504261.5 link	n.264-6790G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000134

AC:

AN:

156628

Hom.:

AF XY:

0.000108

AC XY:

AN XY:

83004

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000183

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000165

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.0000651

AC:

AN:

1398392

Hom.:

Cov.:

AF XY:

0.0000638

AC XY:

AN XY:

689702

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.000252

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000631

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000278

Gnomad4 OTH exome

AF:

0.000138

GnomAD4 genome

AF:

0.000322

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00109

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000229

Hom.:

Bravo

AF:

0.000446

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000788

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1897G>A (p.E633K) alteration is located in exon 15 (coding exon 13) of the ERICH6B gene. This alteration results from a G to A substitution at nucleotide position 1897, causing the glutamic acid (E) at amino acid position 633 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

0.094

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.9

DANN

Benign

0.62

DEOGEN2

Benign

0.012

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.56

M_CAP

Benign

0.0094

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.98

REVEL

Benign

0.033

Sift

Benign

0.070

Sift4G

Uncertain

0.060

Polyphen

0.89

Vest4

0.11

MVP

0.030

ClinPred

0.0057

GERP RS

1.8

Varity_R

0.035

gMVP

0.12

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