NM_001290258.2:c.598G>C

Variant names:

• chr7-123624715-G-C
• NM_001290258.2:c.598G>C
• ASB15 p.Gly200Arg

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001290258.2(ASB15):​c.598G>C​(p.Gly200Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASB15 NM_001290258.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.40
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.955

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.598G>C	p.Gly200Arg	missense	Exon 8 of 12	NP_001277187.1	Q8WXK1
	ASB15	NM_080928.4		c.598G>C	p.Gly200Arg	missense	Exon 6 of 10	NP_563616.3	A0A384NYV2
	ASB15-AS1	NR_111922.1		n.62+181C>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.598G>C	p.Gly200Arg	missense	Exon 8 of 12	ENSP00000416433.1	Q8WXK1
	ASB15	ENST00000447789.5	TSL:1	c.598G>C	p.Gly200Arg	missense	Exon 6 of 7	ENSP00000401166.1	A0A0C4DG46
	ASB15	ENST00000944024.1		c.670G>C	p.Gly224Arg	missense	Exon 8 of 12	ENSP00000614083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.095	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.4
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Uncertain	0.47
Sift	Benign	0.037	D
Sift4G	Uncertain	0.030	D
Varity_R		0.32
gMVP		0.70
Mutation Taster		=77/23	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-123264769;