8-98089418-C-T

Variant summary

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

The NM_173549.3(ERICH5):​c.401C>T​(p.Ala134Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,076 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ERICH5
NM_173549.3 missense

Scores

18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.39
Variant links:
Genes affected
ERICH5 (HGNC:26823): (glutamate rich 5)

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=0.01951465).
BP6
Variant 8-98089418-C-T is Benign according to our data. Variant chr8-98089418-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3276367.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ERICH5NM_173549.3 linkc.401C>T p.Ala134Val missense_variant Exon 2 of 3 ENST00000318528.8 NP_775820.2 Q6P6B1-1
ERICH5NM_001170806.2 linkc.59-3803C>T 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.401C>T p.Ala134Val missense_variant Exon 2 of 3 1 NM_173549.3 ENSP00000315614.3 Q6P6B1-1
ERICH5ENST00000545282.1 linkc.59-3803C>T intron_variant Intron 1 of 1 2 ENSP00000440297.1 Q6P6B1-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461884
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152192
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jun 11, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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
0.092
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
0.073
DANN
Benign
0.82
DEOGEN2
Benign
0.0033
T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0038
N
LIST_S2
Benign
0.51
T
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.020
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.69
N
PROVEAN
Benign
2.7
N
REVEL
Benign
0.022
Sift
Benign
1.0
T
Sift4G
Benign
0.57
T
Polyphen
0.0060
B
Vest4
0.036
MutPred
0.10
Gain of ubiquitination at K131 (P = 0.0641);
MVP
0.040
MPC
0.050
ClinPred
0.040
T
GERP RS
-2.7
Varity_R
0.024
gMVP
0.017

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: rs1815341967; hg19: chr8-99101646; API