Genetic Variant NM_001013842.3:c.406C>T (chr8-22601247-C-T) – ACMG Classification: Benign (-10 pts)

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

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)

C8orf58 links:

ENSG00000248235 (HGNC:):

ENSG00000248235 links:

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
C8orf58	NM_001013842.3 link	c.406C>T	p.Arg136Cys	missense_variant	Exon 2 of 7	ENST00000289989.10	NP_001013864.1	Q8NAV2-1
C8orf58	NM_173686.3 link	c.406C>T	p.Arg136Cys	missense_variant	Exon 2 of 7		NP_775957.2	Q8NAV2-2
C8orf58	NM_001198827.2 link	c.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
C8orf58	ENST00000289989.10 link	c.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:

AN:

152260

Hom.:

Cov.:

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.:

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.:

Cov.:

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:

AN:

152378

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

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.:

Bravo

AF:

0.000540

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000679

AC:

Asia WGS

AF:

0.000289

AC:

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

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

LIST_S2

Benign

0.53

T;T;T;T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.0042

T;T;T;T;T

MetaSVM

Benign

-1.0

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

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.

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