NM_001290258.2:c.355G>C

Variant names:

• chr7-123617641-G-C
• rs759506891
• NM_001290258.2:c.355G>C

Variant summary

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

The NM_001290258.2(ASB15):​c.355G>C​(p.Val119Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000907 in 1,610,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000091 (0 hom.)
• Consequence: ASB15 NM_001290258.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65
• Publications: 0 publications found

Genes affected

ASB15 (HGNC:19767): (ankyrin repeat and SOCS box containing 15) This gene encodes a member of the suppressor of cytokine signaling box superfamily. The proteins in this superfamily participate in the ubiquitin-proteasome system for the degradation of proteins in the cell cycle and signal transduction pathways. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ASB15-AS1 (HGNC:40904): (ASB15 antisense RNA 1)

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=0.2344653).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290258.2. 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
	ASB15	NM_001290258.2	MANE Select	c.355G>C	p.Val119Leu	missense	Exon 7 of 12	NP_001277187.1	Q8WXK1
	ASB15	NM_080928.4		c.355G>C	p.Val119Leu	missense	Exon 5 of 10	NP_563616.3	A0A384NYV2
	ASB15-AS1	NR_111922.1		n.387-2241C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB15	ENST00000451215.6	TSL:2 MANE Select	c.355G>C	p.Val119Leu	missense	Exon 7 of 12	ENSP00000416433.1	Q8WXK1
	ASB15	ENST00000447789.5	TSL:1	c.355G>C	p.Val119Leu	missense	Exon 5 of 7	ENSP00000401166.1	A0A0C4DG46
	ASB15	ENST00000944024.1		c.427G>C	p.Val143Leu	missense	Exon 7 of 12	ENSP00000614083.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000835 AC: 21 AN: 251408 AF XY: 0.0000883

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000912 AC: 133 AN: 1458164 Hom.: 0 Cov.: 30 AF XY: 0.0000937 AC XY: 68 AN XY: 725594

African (AFR) AF: 0.0000300 AC: 1 AN: 33384

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000116 AC: 129 AN: 1108616

Other (OTH) AF: 0.0000332 AC: 2 AN: 60290

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74362

African (AFR) AF: 0.0000241 AC: 1 AN: 41452

American (AMR) AF: 0.000131 AC: 2 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.6
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.21
Sift	Benign	0.090	T
Sift4G	Benign	0.22	T
Polyphen		0.053	B
Vest4		0.56
MVP		0.74
MPC		0.15
ClinPred		0.053	T
GERP RS		0.0086
Varity_R		0.12
gMVP		0.47
Mutation Taster		=95/5	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: rs759506891; hg19: chr7-123257695; COSMIC: COSV51925869; COSMIC: COSV51925869;