NM_001142459.2:c.194G>A

Variant names:

• chr7-151186937-C-T
• rs104886491
• NM_001142459.2:c.194G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001142459.2(ASB10):​c.194G>A​(p.Gly65Glu) 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. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 4.74
• Publications: 1 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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.933

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB10	NM_001142459.2	MANE Select	c.194G>A	p.Gly65Glu	missense	Exon 1 of 6	NP_001135931.2	Q8WXI3-1
	ASB10	NM_001142460.1		c.194G>A	p.Gly65Glu	missense	Exon 1 of 5	NP_001135932.2	Q8WXI3-2
	ASB10	NM_080871.4		c.272-278G>A		intron	N/A	NP_543147.2	Q8WXI3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB10	ENST00000420175.3	TSL:1 MANE Select	c.194G>A	p.Gly65Glu	missense	Exon 1 of 6	ENSP00000391137.2	Q8WXI3-1
	ASB10	ENST00000275838.5	TSL:1	c.194G>A	p.Gly65Glu	missense	Exon 1 of 5	ENSP00000275838.1	Q8WXI3-2
	ASB10	ENST00000968508.1		c.194G>A	p.Gly65Glu	missense	Exon 1 of 6	ENSP00000638567.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.7
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.57
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.94
MVP		0.61
MPC		0.37
ClinPred		0.99	D
GERP RS		4.4
PromoterAI		0.011	Neutral
Varity_R		0.62
gMVP		0.75
Mutation Taster		=58/42	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

Other links and lift over

dbSNP: rs104886491; hg19: chr7-150884024;