rs151344610

chr7-151181085-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001142459.2(ASB10):c.958G>A(p.Ala320Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,612,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 3.17

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11307156).
• BS2: High AC in GnomAd at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASB10	NM_001142459.2	c.958G>A	p.Ala320Thr	missense_variant	3/6	ENST00000420175.3
ASB10	NM_080871.4	c.913G>A	p.Ala305Thr	missense_variant	3/6
ASB10	NM_001142460.1	c.958G>A	p.Ala320Thr	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB10	ENST00000420175.3	c.958G>A	p.Ala320Thr	missense_variant	3/6	1	NM_001142459.2	P4
ASB10	ENST00000275838.5	c.958G>A	p.Ala320Thr	missense_variant	3/5	1
ASB10	ENST00000377867.7	c.913G>A	p.Ala305Thr	missense_variant	3/6	2		A1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000154 AC: 38 AN: 246982 Hom.: 0 AF XY: 0.000141 AC XY: 19 AN XY: 134588

Gnomad AFR exome AF: 0.0000631

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000589

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000906

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000105 AC: 153 AN: 1460126 Hom.: 0 Cov.: 31 AF XY: 0.000116 AC XY: 84 AN XY: 726384

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000557

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000782

Gnomad4 OTH exome AF: 0.0000828

GnomAD4 genome AF: 0.0000656 AC: 10 AN: 152350 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74502

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000642

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000148 AC: 18

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Glaucoma 1, open angle, F Other:1

not provided, no classification provided

literature only

Casey Eye Institute Glaucoma Genetics Lab

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	18
Dann	Uncertain	0.98
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.69	T;T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;L
MutationTaster	Benign	0.96	N;N;N;N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.081
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.087	T;T;T
Polyphen		0.97, 0.97	.;D;D
Vest4		0.16
MVP		0.38
MPC		0.056
ClinPred		0.062	T
GERP RS		2.6
Varity_R		0.046
gMVP		0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs151344610; hg19: chr7-150878172; COSMIC: COSV51998649;