8-22601247-C-T

Variant names:

• chr8-22601247-C-T
• rs202142296
• NM_001013842.3:c.406C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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. 14/20 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.78
• Publications: 3 publications found

Genes affected

C8orf58 (HGNC:32233): (chromosome 8 open reading frame 58)

ENSG00000248235 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 2658469.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C8orf58	NM_001013842.3	MANE Select	c.406C>T	p.Arg136Cys	missense	Exon 2 of 7	NP_001013864.1	Q8NAV2-1
	C8orf58	NM_173686.3		c.406C>T	p.Arg136Cys	missense	Exon 2 of 7	NP_775957.2
	C8orf58	NM_001198827.2		c.406C>T	p.Arg136Cys	missense	Exon 2 of 6	NP_001185756.1	A0A087WX44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C8orf58	ENST00000289989.10	TSL:5 MANE Select	c.406C>T	p.Arg136Cys	missense	Exon 2 of 7	ENSP00000289989.5	Q8NAV2-1
	C8orf58	ENST00000905139.1		c.406C>T	p.Arg136Cys	missense	Exon 2 of 6	ENSP00000575198.1
	C8orf58	ENST00000905138.1		c.406C>T	p.Arg136Cys	missense	Exon 2 of 5	ENSP00000575197.1

Frequencies

GnomAD3 genomes AF: 0.000486 AC: 74 AN: 152260 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.000832 AC: 202 AN: 242780 AF XY: 0.000891

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 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

African (AFR) AF: 0.000209 AC: 7 AN: 33420

American (AMR) AF: 0.000405 AC: 18 AN: 44438

Ashkenazi Jewish (ASJ) AF: 0.0100 AC: 262 AN: 26072

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39488

South Asian (SAS) AF: 0.00106 AC: 91 AN: 85812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51948

Middle Eastern (MID) AF: 0.0106 AC: 60 AN: 5646

European-Non Finnish (NFE) AF: 0.000252 AC: 280 AN: 1110342

Other (OTH) AF: 0.00136 AC: 82 AN: 60176

GnomAD4 genome AF: 0.000486 AC: 74 AN: 152378 Hom.: 0 Cov.: 33 AF XY: 0.000456 AC XY: 34 AN XY: 74524

African (AFR) AF: 0.0000962 AC: 4 AN: 41588

American (AMR) AF: 0.000261 AC: 4 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 38 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68036

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00104 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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-4.8
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.052
Sift	Benign	0.13	T
Sift4G	Benign	0.12	T
Polyphen		0.025	B
Vest4		0.11
MVP		0.22
MPC		0.052
ClinPred		0.027	T
GERP RS		-0.48
Varity_R		0.050
gMVP		0.059
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs202142296; hg19: chr8-22458760; COSMIC: COSV51514343; COSMIC: COSV51514343;