8-98089191-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173549.3(ERICH5):​c.174C>A​(p.Ser58Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ERICH5
NM_173549.3 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.266
Variant links:
Genes affected
ERICH5 (HGNC:26823): (glutamate rich 5)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08742133).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ERICH5NM_173549.3 linkc.174C>A p.Ser58Arg missense_variant Exon 2 of 3 ENST00000318528.8 NP_775820.2 Q6P6B1-1
ERICH5NM_001170806.2 linkc.59-4030C>A intron_variant Intron 1 of 1 NP_001164277.1 Q6P6B1-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ERICH5ENST00000318528.8 linkc.174C>A p.Ser58Arg missense_variant Exon 2 of 3 1 NM_173549.3 ENSP00000315614.3 Q6P6B1-1
ERICH5ENST00000545282.1 linkc.59-4030C>A intron_variant Intron 1 of 1 2 ENSP00000440297.1 Q6P6B1-2

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152196
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251474
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1461894
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.000388
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152196
Hom.:
0
Cov.:
33
AF XY:
0.0000941
AC XY:
7
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000579
Hom.:
0
Bravo
AF:
0.000102
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 26, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.174C>A (p.S58R) alteration is located in exon 2 (coding exon 2) of the ERICH5 gene. This alteration results from a C to A substitution at nucleotide position 174, causing the serine (S) at amino acid position 58 to be replaced by an arginine (R). 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
0.24
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
11
DANN
Uncertain
0.98
DEOGEN2
Benign
0.092
T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.47
T
M_CAP
Benign
0.0092
T
MetaRNN
Benign
0.087
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
PROVEAN
Uncertain
-4.3
D
REVEL
Benign
0.11
Sift
Uncertain
0.0040
D
Sift4G
Benign
0.074
T
Polyphen
0.93
P
Vest4
0.23
MutPred
0.17
Loss of phosphorylation at S58 (P = 0.0121);
MVP
0.23
MPC
0.063
ClinPred
0.38
T
GERP RS
0.058
Varity_R
0.33
gMVP
0.10

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: rs144887662; hg19: chr8-99101419; API