chr13-45541656-C-T

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

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00600
Variant links:
Genes affected
ERICH6B (HGNC:26523): (glutamate rich 6B)

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
ERICH6BNM_182542.3 linkc.1897G>A p.Glu633Lys missense_variant Exon 15 of 15 ENST00000298738.3 NP_872348.2 Q5W0A0-1
ERICH6BXM_011534965.3 linkc.1969G>A p.Glu657Lys missense_variant Exon 14 of 14 XP_011533267.1
ERICH6BXM_017020418.2 linkc.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
ERICH6BENST00000298738.3 linkc.1897G>A p.Glu633Lys missense_variant Exon 15 of 15 2 NM_182542.3 ENSP00000298738.2 Q5W0A0-1
ERICH6BENST00000504261.5 linkn.264-6790G>A intron_variant Intron 2 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.000322
AC:
49
AN:
152122
Hom.:
0
Cov.:
32
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:
21
AN:
156628
Hom.:
0
AF XY:
0.000108
AC XY:
9
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:
91
AN:
1398392
Hom.:
0
Cov.:
34
AF XY:
0.0000638
AC XY:
44
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:
49
AN:
152122
Hom.:
0
Cov.:
32
AF XY:
0.000336
AC XY:
25
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.:
0
Bravo
AF:
0.000446
ESP6500AA
AF:
0.000723
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000788
AC:
2

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
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
9.9
DANN
Benign
0.62
DEOGEN2
Benign
0.012
T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.0094
T
MetaRNN
Benign
0.027
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.81
L
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.98
N
REVEL
Benign
0.033
Sift
Benign
0.070
T
Sift4G
Uncertain
0.060
T
Polyphen
0.89
P
Vest4
0.11
MVP
0.030
ClinPred
0.0057
T
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.

Other links and lift over

dbSNP: rs368780411; hg19: chr13-46115791; COSMIC: COSV53918357; COSMIC: COSV53918357; API