ASB15 p.Met69Ile

Variant names:

• chr7-123616410-G-T
• NM_001290258.2:c.207G>T
• ASB15 p.Met69Ile

Your query was ambiguous. Multiple possible variants found:

• chr7-123616410-G-T
• chr7-123616410-G-C
• chr7-123616410-G-A

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.207G>T​(p.Met69Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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 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: 1.28
• 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=0.09359759).

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.207G>T	p.Met69Ile	missense	Exon 6 of 12	NP_001277187.1	Q8WXK1
	ASB15	NM_080928.4		c.207G>T	p.Met69Ile	missense	Exon 4 of 10	NP_563616.3	A0A384NYV2
	ASB15-AS1	NR_111922.1		n.387-1010C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB15	ENST00000451215.6	TSL:2 MANE Select	c.207G>T	p.Met69Ile	missense	Exon 6 of 12	ENSP00000416433.1	Q8WXK1
	ASB15	ENST00000447789.5	TSL:1	c.207G>T	p.Met69Ile	missense	Exon 4 of 7	ENSP00000401166.1	A0A0C4DG46
	ASB15	ENST00000944024.1		c.279G>T	p.Met93Ile	missense	Exon 6 of 12	ENSP00000614083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.3
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.057
Sift	Uncertain	0.020	D
Sift4G	Benign	0.40	T
Varity_R		0.27
gMVP		0.17
Mutation Taster		=96/4	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

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

Other links and lift over

hg19: chr7-123256464;