7-151186412-G-T

Position:

• chr7-151186412-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001142459.2(ASB10):​c.564C>A​(p.Cys188*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. 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). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ASB10 NM_001142459.2 stop_gained
• Clinical Significance: not provided no classification provided P:1 O:1
• Conservation: PhyloP100: 1.46

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-151186412-G-T is Pathogenic according to our data. Variant chr7-151186412-G-T is described in ClinVar as [not_provided]. Clinvar id is 50952.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=1, not_provided=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.564C>A	p.Cys188*	stop_gained	2/6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4	c.519C>A	p.Cys173*	stop_gained	2/6		NP_543147.2
ASB10	NM_001142460.1	c.564C>A	p.Cys188*	stop_gained	2/5		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3	c.564C>A	p.Cys188*	stop_gained	2/6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5	c.564C>A	p.Cys188*	stop_gained	2/5	1		ENSP00000275838.1
ASB10	ENST00000377867.7	c.519C>A	p.Cys173*	stop_gained	2/6	2		ENSP00000367098.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1434574 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 711036

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Pathogenic:1 Other:1

Revision: no classification provided

Submissions by phenotype

Glaucoma 1, open angle, F Pathogenic:1 Other:1

not provided, no classification provided	literature only	Casey Eye Institute Glaucoma Genetics Lab	-	- -
Pathogenic, flagged submission	literature only	OMIM	Mar 15, 2012	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.95	D
Vest4		0.28
GERP RS		3.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs151344606; hg19: chr7-150883499;