8-22601247-C-A

Variant names:

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

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.406C>A​(p.Arg136Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. R136C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: C8orf58 NM_001013842.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: 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=0.0688867).

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>A	p.Arg136Ser	missense	Exon 2 of 7	NP_001013864.1	Q8NAV2-1
	C8orf58	NM_173686.3		c.406C>A	p.Arg136Ser	missense	Exon 2 of 7	NP_775957.2
	C8orf58	NM_001198827.2		c.406C>A	p.Arg136Ser	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>A	p.Arg136Ser	missense	Exon 2 of 7	ENSP00000289989.5	Q8NAV2-1
	C8orf58	ENST00000905139.1		c.406C>A	p.Arg136Ser	missense	Exon 2 of 6	ENSP00000575198.1
	C8orf58	ENST00000905138.1		c.406C>A	p.Arg136Ser	missense	Exon 2 of 5	ENSP00000575197.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457344 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724526

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 44438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39488

South Asian (SAS) AF: 0.00 AC: 0 AN: 85812

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5648

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110342

Other (OTH) AF: 0.00 AC: 0 AN: 60176

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.0070
DANN	Benign	0.76
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-4.8
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.066
Sift	Benign	0.78	T
Sift4G	Benign	0.61	T
Polyphen		0.60	P
Vest4		0.21
MutPred		0.20		Gain of phosphorylation at R136 (P = 0.0135)
MVP		0.030
MPC		0.047
ClinPred		0.16	T
GERP RS		-0.48
Varity_R		0.071
gMVP		0.071
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;