Genetic Variant NM_001013842.3:c.701C>T (chr8-22602015-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001013842.3(C8orf58):c.701C>T(p.Pro234Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000698 in 1,576,232 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

C8orf58
NM_001013842.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.618

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029872507).

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.701C>T	p.Pro234Leu	missense	Exon 4 of 7	NP_001013864.1	Q8NAV2-1
C8orf58	NM_173686.3		c.701C>T	p.Pro234Leu	missense	Exon 4 of 7	NP_775957.2
C8orf58	NM_001198827.2		c.701C>T	p.Pro234Leu	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.701C>T	p.Pro234Leu	missense	Exon 4 of 7	ENSP00000289989.5	Q8NAV2-1
C8orf58	ENST00000905139.1		c.701C>T	p.Pro234Leu	missense	Exon 4 of 6	ENSP00000575198.1
C8orf58	ENST00000905138.1		c.701C>T	p.Pro234Leu	missense	Exon 4 of 5	ENSP00000575197.1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000119

AC:

AN:

218924

AF XY:

0.000110

show subpopulations

Gnomad AFR exome

AF:

0.000139

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00206

Gnomad EAS exome

AF:

0.000115

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000409

Gnomad OTH exome

AF:

0.000376

GnomAD4 exome

AF:

0.0000660

AC:

AN:

1423966

Hom.:

Cov.:

AF XY:

0.0000626

AC XY:

AN XY:

703086

show subpopulations

African (AFR)

AF:

0.000215

AC:

AN:

32618

American (AMR)

AF:

0.0000476

AC:

AN:

42016

Ashkenazi Jewish (ASJ)

AF:

0.00216

AC:

AN:

24124

East Asian (EAS)

AF:

0.000129

AC:

AN:

38730

South Asian (SAS)

AF:

0.00

AC:

AN:

81804

European-Finnish (FIN)

AF:

0.0000197

AC:

AN:

50862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.0000138

AC:

AN:

1089610

Other (OTH)

AF:

0.000205

AC:

AN:

58558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000105

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41560

American (AMR)

AF:

0.000131

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000183

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000662

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.065

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.68

M_CAP

Benign

0.021

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

PhyloP100

0.62

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.13

Sift

Benign

0.47

Sift4G

Uncertain

0.013

Polyphen

0.45

Vest4

0.12

MVP

0.35

MPC

0.048

ClinPred

0.032

GERP RS

3.2

PromoterAI

0.013

Neutral

(source)

Varity_R

0.047

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