9-129638083-T-C

Variant names:

• chr9-129638083-T-C
• NM_017873.4:c.973A>G

Variant summary

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

The NM_017873.4(ASB6):​c.973A>G​(p.Lys325Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ASB6 NM_017873.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.71
• Publications: 0 publications found

Genes affected

ASB6 (HGNC:17181): (ankyrin repeat and SOCS box containing 6) The protein encoded by this gene belongs to a family of ankyrin repeat proteins that, along with four other protein families, contain a C-terminal SOCS box motif. Growing evidence suggests that the SOCS box, similar to the F-box, acts as a bridge between specific substrate-binding domains and the more generic proteins that comprise a large family of E3 ubiquitin protein ligases. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jan 2011]

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=0.2756039).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017873.4. 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
	ASB6	NM_017873.4	MANE Select	c.973A>G	p.Lys325Glu	missense	Exon 6 of 6	NP_060343.1	Q9NWX5-1
	ASB6	NM_001202403.2		c.886A>G	p.Lys296Glu	missense	Exon 5 of 5	NP_001189332.1	F6TX30
	ASB6	NM_177999.3		c.*270A>G		3_prime_UTR	Exon 5 of 5	NP_821066.1	Q9NWX5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB6	ENST00000277458.5	TSL:1 MANE Select	c.973A>G	p.Lys325Glu	missense	Exon 6 of 6	ENSP00000277458.4	Q9NWX5-1
	ASB6	ENST00000450050.6	TSL:1	c.886A>G	p.Lys296Glu	missense	Exon 5 of 5	ENSP00000416172.3	F6TX30
	ASB6	ENST00000277459.8	TSL:1	c.*270A>G		3_prime_UTR	Exon 5 of 5	ENSP00000277459.4	Q9NWX5-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

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	0.27
BayesDel_addAF	Benign	0.0085	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.032
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.14
Sift	Benign	0.10	T
Sift4G	Uncertain	0.056	T
Polyphen		0.13	B
Vest4		0.42
MutPred		0.42		Loss of ubiquitination at K325 (P = 0.0297)
MVP		0.74
MPC		1.3
ClinPred		0.82	D
GERP RS		5.1
Varity_R		0.15
gMVP		0.42
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr9-132400362;