8-22602015-C-G

Variant names:

• chr8-22602015-C-G
• rs139447220
• NM_001013842.3:c.701C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013842.3(C8orf58):​c.701C>G​(p.Pro234Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000571 in 1,576,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P234L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: C8orf58 NM_001013842.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618
• Publications: 0 publications found

Genes affected

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

ENSG00000248235 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13494787).

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.701C>G	p.Pro234Arg	missense	Exon 4 of 7	NP_001013864.1	Q8NAV2-1
	C8orf58	NM_173686.3		c.701C>G	p.Pro234Arg	missense	Exon 4 of 7	NP_775957.2
	C8orf58	NM_001198827.2		c.701C>G	p.Pro234Arg	missense	Exon 4 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.701C>G	p.Pro234Arg	missense	Exon 4 of 7	ENSP00000289989.5	Q8NAV2-1
	C8orf58	ENST00000905139.1		c.701C>G	p.Pro234Arg	missense	Exon 4 of 6	ENSP00000575198.1
	C8orf58	ENST00000905138.1		c.701C>G	p.Pro234Arg	missense	Exon 4 of 5	ENSP00000575197.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000914 AC: 2 AN: 218924 AF XY: 0.00000845

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000315

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000102

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000492 AC: 7 AN: 1423970 Hom.: 0 Cov.: 33 AF XY: 0.00000427 AC XY: 3 AN XY: 703090

African (AFR) AF: 0.00 AC: 0 AN: 32618

American (AMR) AF: 0.0000238 AC: 1 AN: 42016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24128

East Asian (EAS) AF: 0.00 AC: 0 AN: 38730

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 0.00000459 AC: 5 AN: 1089610

Other (OTH) AF: 0.00 AC: 0 AN: 58558

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00000913 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.62
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.15
Sift	Benign	0.054	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.13
MutPred		0.15		Gain of MoRF binding (P = 0.0305)
MVP		0.15
MPC		0.29
ClinPred		0.85	D
GERP RS		3.2
PromoterAI		-0.018	Neutral
Varity_R		0.10
gMVP		0.16
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs139447220; hg19: chr8-22459528;