Genetic Variant C8orf58:p.Pro221Ser (chr8-22601975-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.661C>T(p.Pro221Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00808 in 1,552,242 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0068 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0082 ( 80 hom. )

Consequence

C8orf58
NM_001013842.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0730

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=0.003995776).

BP6

Variant 8-22601975-C-T is Benign according to our data. Variant chr8-22601975-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658470.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C8orf58	NM_001013842.3 link	c.661C>T	p.Pro221Ser	missense_variant	Exon 4 of 7	ENST00000289989.10	NP_001013864.1	Q8NAV2-1
C8orf58	NM_173686.3 link	c.661C>T	p.Pro221Ser	missense_variant	Exon 4 of 7		NP_775957.2	Q8NAV2-2
C8orf58	NM_001198827.2 link	c.661C>T	p.Pro221Ser	missense_variant	Exon 4 of 6		NP_001185756.1	A0A087WX44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C8orf58	ENST00000289989.10 link	c.661C>T	p.Pro221Ser	missense_variant	Exon 4 of 7	5	NM_001013842.3	ENSP00000289989.5		Q8NAV2-1

Frequencies

GnomAD3 genomes

AF:

0.00686

AC:

1044

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0234

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00940

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00771

AC:

1581

AN:

205136

Hom.:

AF XY:

0.00785

AC XY:

861

AN XY:

109712

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.00199

Gnomad ASJ exome

AF:

0.00460

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00190

Gnomad FIN exome

AF:

0.0272

Gnomad NFE exome

AF:

0.00968

Gnomad OTH exome

AF:

0.00914

GnomAD4 exome

AF:

0.00821

AC:

11499

AN:

1399972

Hom.:

Cov.:

AF XY:

0.00817

AC XY:

5620

AN XY:

688304

show subpopulations

Gnomad4 AFR exome

AF:

0.00141

Gnomad4 AMR exome

AF:

0.00289

Gnomad4 ASJ exome

AF:

0.00505

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00214

Gnomad4 FIN exome

AF:

0.0271

Gnomad4 NFE exome

AF:

0.00850

Gnomad4 OTH exome

AF:

0.00815

GnomAD4 genome

AF:

0.00685

AC:

1043

AN:

152270

Hom.:

Cov.:

AF XY:

0.00731

AC XY:

544

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0234

Gnomad4 NFE

AF:

0.00940

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00808

Hom.:

Bravo

AF:

0.00517

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00838

AC:

ExAC

AF:

0.00756

AC:

913

Asia WGS

AF:

0.000577

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

0.085

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;.;.;T;.;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.79

T;T;T;T;T;T

MetaRNN

Benign

0.0040

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L;.;L;.;.

PROVEAN

Pathogenic

-4.7

.;D;.;D;.;D

REVEL

Benign

0.074

Sift

Uncertain

0.026

.;D;.;D;.;D

Sift4G

Benign

0.15

T;D;T;T;D;D

Polyphen

0.71

.;P;.;P;.;.

Vest4

0.18, 0.19, 0.21, 0.17

MVP

0.11

MPC

0.071

ClinPred

0.037

GERP RS

1.6

Varity_R

0.14

gMVP

0.13

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.

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