7-151176198-T-C

Variant names:

• chr7-151176198-T-C
• rs104886487
• NM_001142459.2:c.1318A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142459.2(ASB10):​c.1318A>G​(p.Ser440Gly) 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. 16/22 in silico tools predict a benign outcome for this variant. 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. S440I) 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: 0.465
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07283047).

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.1318A>G	p.Ser440Gly	missense	Exon 5 of 6	NP_001135931.2
	ASB10	NM_080871.4		c.1273A>G	p.Ser425Gly	missense	Exon 5 of 6	NP_543147.2
	ASB10	NM_001142460.1		c.1204A>G	p.Ser402Gly	missense	Exon 4 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.1318A>G	p.Ser440Gly	missense	Exon 5 of 6	ENSP00000391137.2
	ASB10	ENST00000275838.5	TSL:1	c.1204A>G	p.Ser402Gly	missense	Exon 4 of 5	ENSP00000275838.1
	ASB10	ENST00000377867.7	TSL:2	c.1273A>G	p.Ser425Gly	missense	Exon 5 of 6	ENSP00000367098.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Glaucoma 1, open angle, F Other:1

Casey Eye Institute Glaucoma Genetics Lab

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.3
DANN	Benign	0.91
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.93	L
PhyloP100		0.47
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.017
Sift	Benign	0.19	T
Sift4G	Benign	0.15	T
Polyphen		0.16	B
Vest4		0.13
MVP		0.13
MPC		0.071
ClinPred		0.22	T
GERP RS		-0.93
Varity_R		0.086
gMVP		0.29
Mutation Taster		=97/3	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: rs104886487; hg19: chr7-150873285;