Genetic Variant C8orf58:p.Pro221Ser (chr8-22601975-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 12/19 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

Publications

9 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2658470.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013842.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C8orf58	NM_001013842.3	MANE Select	c.661C>T	p.Pro221Ser	missense	Exon 4 of 7	NP_001013864.1	Q8NAV2-1
C8orf58	NM_173686.3		c.661C>T	p.Pro221Ser	missense	Exon 4 of 7	NP_775957.2
C8orf58	NM_001198827.2		c.661C>T	p.Pro221Ser	missense	Exon 4 of 6	NP_001185756.1	A0A087WX44

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C8orf58	ENST00000289989.10	TSL:5 MANE Select	c.661C>T	p.Pro221Ser	missense	Exon 4 of 7	ENSP00000289989.5	Q8NAV2-1
C8orf58	ENST00000905139.1		c.661C>T	p.Pro221Ser	missense	Exon 4 of 6	ENSP00000575198.1
C8orf58	ENST00000905138.1		c.661C>T	p.Pro221Ser	missense	Exon 4 of 5	ENSP00000575197.1

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

GnomAD2 exomes

AF:

0.00771

AC:

1581

AN:

205136

AF XY:

0.00785

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 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

African (AFR)

AF:

0.00141

AC:

AN:

31960

American (AMR)

AF:

0.00289

AC:

113

AN:

39072

Ashkenazi Jewish (ASJ)

AF:

0.00505

AC:

112

AN:

22162

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38928

South Asian (SAS)

AF:

0.00214

AC:

166

AN:

77460

European-Finnish (FIN)

AF:

0.0271

AC:

1351

AN:

49766

Middle Eastern (MID)

AF:

0.0152

AC:

AN:

5474

European-Non Finnish (NFE)

AF:

0.00850

AC:

9159

AN:

1077610

Other (OTH)

AF:

0.00815

AC:

469

AN:

57540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

606

1211

1817

2422

3028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

332

664

996

1328

1660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00685

AC:

1043

AN:

152270

Hom.:

Cov.:

AF XY:

0.00731

AC XY:

544

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00147

AC:

AN:

41554

American (AMR)

AF:

0.00405

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00166

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0234

AC:

249

AN:

10622

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00940

AC:

639

AN:

67994

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

106

160

213

266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00747

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

-0.073

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.074

Sift

Uncertain

0.026

Sift4G

Benign

0.15

Polyphen

0.71

Vest4

0.18

MVP

0.11

MPC

0.071

ClinPred

0.037

GERP RS

1.6

PromoterAI

0.0046

Neutral

(source)

Varity_R

0.14

gMVP

0.13

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over