chr8-22601247-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001013842.3(C8orf58):​c.406C>T​(p.Arg136Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000544 in 1,609,720 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R136H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00055 ( 3 hom. )

Consequence

C8orf58
NM_001013842.3 missense

Scores

1
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.78
Variant links:
Genes affected
C8orf58 (HGNC:32233): (chromosome 8 open reading frame 58)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0041614175).
BP6
Variant 8-22601247-C-T is Benign according to our data. Variant chr8-22601247-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658469.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C8orf58NM_001013842.3 linkc.406C>T p.Arg136Cys missense_variant Exon 2 of 7 ENST00000289989.10 NP_001013864.1 Q8NAV2-1
C8orf58NM_173686.3 linkc.406C>T p.Arg136Cys missense_variant Exon 2 of 7 NP_775957.2 Q8NAV2-2
C8orf58NM_001198827.2 linkc.406C>T p.Arg136Cys missense_variant Exon 2 of 6 NP_001185756.1 A0A087WX44

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C8orf58ENST00000289989.10 linkc.406C>T p.Arg136Cys missense_variant Exon 2 of 7 5 NM_001013842.3 ENSP00000289989.5 Q8NAV2-1

Frequencies

GnomAD3 genomes
AF:
0.000486
AC:
74
AN:
152260
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.0109
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000620
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.000832
AC:
202
AN:
242780
Hom.:
3
AF XY:
0.000891
AC XY:
118
AN XY:
132494
show subpopulations
Gnomad AFR exome
AF:
0.0000654
Gnomad AMR exome
AF:
0.000206
Gnomad ASJ exome
AF:
0.0104
Gnomad EAS exome
AF:
0.0000559
Gnomad SAS exome
AF:
0.000900
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000432
Gnomad OTH exome
AF:
0.00286
GnomAD4 exome
AF:
0.000550
AC:
801
AN:
1457342
Hom.:
3
Cov.:
32
AF XY:
0.000588
AC XY:
426
AN XY:
724526
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.000405
Gnomad4 ASJ exome
AF:
0.0100
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00106
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000252
Gnomad4 OTH exome
AF:
0.00136
GnomAD4 genome
AF:
0.000486
AC:
74
AN:
152378
Hom.:
0
Cov.:
33
AF XY:
0.000456
AC XY:
34
AN XY:
74524
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.0109
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00117
Hom.:
2
Bravo
AF:
0.000540
ESP6500AA
AF:
0.000228
AC:
1
ESP6500EA
AF:
0.000466
AC:
4
ExAC
AF:
0.000679
AC:
82
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Oct 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

C8orf58: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
0.076
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
.;.;.;T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.023
N
LIST_S2
Benign
0.53
T;T;T;T;T
M_CAP
Benign
0.0057
T
MetaRNN
Benign
0.0042
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
.;N;.;N;.
PROVEAN
Benign
-1.2
.;N;.;N;.
REVEL
Benign
0.052
Sift
Benign
0.13
.;T;.;T;.
Sift4G
Benign
0.12
T;T;T;T;T
Polyphen
0.025
.;B;.;B;.
Vest4
0.11, 0.080, 0.059, 0.079
MVP
0.22
MPC
0.052
ClinPred
0.027
T
GERP RS
-0.48
Varity_R
0.050
gMVP
0.059

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs202142296; hg19: chr8-22458760; COSMIC: COSV51514343; COSMIC: COSV51514343; API