chr7-123614540-C-A

Variant names:

• chr7-123614540-C-A
• rs1168993644
• NM_001290258.2:c.38C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001290258.2(ASB15):​c.38C>A​(p.Thr13Lys) 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 1,458,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ASB15 NM_001290258.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.19
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2753539).

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.38C>A	p.Thr13Lys	missense	Exon 4 of 12	NP_001277187.1	Q8WXK1
	ASB15	NM_080928.4		c.38C>A	p.Thr13Lys	missense	Exon 2 of 10	NP_563616.3	A0A384NYV2
	ASB15-AS1	NR_111922.1		n.480-304G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB15	ENST00000451215.6	TSL:2 MANE Select	c.38C>A	p.Thr13Lys	missense	Exon 4 of 12	ENSP00000416433.1	Q8WXK1
	ASB15	ENST00000447789.5	TSL:1	c.38C>A	p.Thr13Lys	missense	Exon 2 of 7	ENSP00000401166.1	A0A0C4DG46
	ASB15	ENST00000944024.1		c.38C>A	p.Thr13Lys	missense	Exon 3 of 12	ENSP00000614083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458004 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 725552

African (AFR) AF: 0.00 AC: 0 AN: 33380

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 86094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108828

Other (OTH) AF: 0.00 AC: 0 AN: 60278

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.21
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.97
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.2
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.061	T
Polyphen		0.19	B
Vest4		0.63
MutPred		0.41		Gain of ubiquitination at T13 (P = 0.0101)
MVP		0.74
MPC		0.30
ClinPred		0.80	D
GERP RS		6.0
Varity_R		0.19
gMVP		0.36
Mutation Taster		=72/28	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: rs1168993644; hg19: chr7-123254594;