chr7-151186429-G-T

Variant names:

• chr7-151186429-G-T
• rs151344605
• NM_001142459.2:c.547C>A

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.547C>A​(p.Arg183Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R183C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• 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=0.14274815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.547C>A	p.Arg183Ser	missense_variant	Exon 2 of 6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4	c.502C>A	p.Arg168Ser	missense_variant	Exon 2 of 6		NP_543147.2
ASB10	NM_001142460.1	c.547C>A	p.Arg183Ser	missense_variant	Exon 2 of 5		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3	c.547C>A	p.Arg183Ser	missense_variant	Exon 2 of 6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5	c.547C>A	p.Arg183Ser	missense_variant	Exon 2 of 5	1		ENSP00000275838.1
ASB10	ENST00000377867.7	c.502C>A	p.Arg168Ser	missense_variant	Exon 2 of 6	2		ENSP00000367098.3
ASB10	ENST00000415615.1	n.*591C>A		downstream_gene_variant		4		ENSP00000410871.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436054 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 711874

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32912

American (AMR) AF: 0.0000244 AC: 1 AN: 40996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25600

East Asian (EAS) AF: 0.00 AC: 0 AN: 38302

South Asian (SAS) AF: 0.00 AC: 0 AN: 82422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099572

Other (OTH) AF: 0.00 AC: 0 AN: 59426

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.84
DEOGEN2	Benign	0.017	.;.;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.83	T;D;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N;.;N
PhyloP100		1.4
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.35	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.83	T;T;T
Sift4G	Benign	0.75	T;T;T
Polyphen		0.16, 0.011	.;B;B
Vest4		0.48
MVP		0.53
MPC		0.060
ClinPred		0.14	T
GERP RS		3.1
Varity_R		0.19
gMVP		0.43
Mutation Taster		=94/6	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: rs151344605; hg19: chr7-150883516;