rs104886482

Variant names:

• chr7-151181047-G-C
• rs104886482
• NM_001142459.2:c.996C>G

Variant summary

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

The NM_001142459.2(ASB10):​c.996C>G​(p.His332Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H332P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 1.90
• Publications: 0 publications found

Genes affected

ASB10 (HGNC:17185): (ankyrin repeat and SOCS box containing 10) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. The SOCS box serves to couple suppressor of cytokine signaling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2008]

ASB10 Gene-Disease associations (from GenCC):

• glaucoma 1, open angle, F

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142459.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB10	NM_001142459.2	MANE Select	c.996C>G	p.His332Gln	missense	Exon 3 of 6	NP_001135931.2
	ASB10	NM_080871.4		c.951C>G	p.His317Gln	missense	Exon 3 of 6	NP_543147.2
	ASB10	NM_001142460.1		c.996C>G	p.His332Gln	missense	Exon 3 of 5	NP_001135932.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB10	ENST00000420175.3	TSL:1 MANE Select	c.996C>G	p.His332Gln	missense	Exon 3 of 6	ENSP00000391137.2
	ASB10	ENST00000275838.5	TSL:1	c.996C>G	p.His332Gln	missense	Exon 3 of 5	ENSP00000275838.1
	ASB10	ENST00000377867.7	TSL:2	c.951C>G	p.His317Gln	missense	Exon 3 of 6	ENSP00000367098.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	Glaucoma 1, open angle, F (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	0.058
Eigen_PC	Benign	0.012
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.9
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.47
Sift	Benign	0.12	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.61
MVP		0.52
MPC		0.092
ClinPred		0.49	T
GERP RS		1.6
Varity_R		0.16
gMVP		0.60
Mutation Taster		=49/51	disease causing

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: rs104886482; hg19: chr7-150878134;