X-15293257-C-T

Variant names:

• chrX-15293257-C-T
• rs151024633
• NM_080873.3:c.433G>A

Variant summary

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

The NM_080873.3(ASB11):​c.433G>A​(p.Ala145Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,210,100 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.000031 (0 hom. 14 hem.)
• Consequence: ASB11 NM_080873.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.38

Genes affected

ASB11 (HGNC:17186): (ankyrin repeat and SOCS box containing 11) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15282288).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB11	NM_080873.3	c.433G>A	p.Ala145Thr	missense_variant	Exon 4 of 7	ENST00000480796.6	NP_543149.1
ASB11	NM_001201583.2	c.382G>A	p.Ala128Thr	missense_variant	Exon 4 of 7		NP_001188512.1
ASB11	NM_001012428.2	c.370G>A	p.Ala124Thr	missense_variant	Exon 4 of 7		NP_001012428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB11	ENST00000480796.6	c.433G>A	p.Ala145Thr	missense_variant	Exon 4 of 7	1	NM_080873.3	ENSP00000417914.1
ASB11	ENST00000380470.7	c.382G>A	p.Ala128Thr	missense_variant	Exon 4 of 7	1		ENSP00000369837.3
ASB11	ENST00000485437.2	n.433G>A		non_coding_transcript_exon_variant	Exon 4 of 8	1		ENSP00000419385.2
ASB11	ENST00000344384.8	c.370G>A	p.Ala124Thr	missense_variant	Exon 4 of 7	5		ENSP00000343408.4

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 14 AN: 112210 Hom.: 0 Cov.: 23 AF XY: 0.0000582 AC XY: 2 AN XY: 34362

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00729

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000169

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000274 AC: 5 AN: 182475 Hom.: 0 AF XY: 0.0000298 AC XY: 2 AN XY: 67019

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000310 AC: 34 AN: 1097890 Hom.: 0 Cov.: 30 AF XY: 0.0000385 AC XY: 14 AN XY: 363252

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: 0.0000404

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000125 AC: 14 AN: 112210 Hom.: 0 Cov.: 23 AF XY: 0.0000582 AC XY: 2 AN XY: 34362

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000169

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000214 Hom.: 1

Bravo AF: 0.000125

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000546

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.433G>A (p.A145T) alteration is located in exon 4 (coding exon 4) of the ASB11 gene. This alteration results from a G to A substitution at nucleotide position 433, causing the alanine (A) at amino acid position 145 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	.;.;T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Pathogenic	0.68	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.78	.;.;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.28
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.50	T;T;T
Polyphen		1.0	.;.;D
Vest4		0.41
MVP		0.73
MPC		0.24
ClinPred		0.26	T
GERP RS		5.3
Varity_R		0.38
gMVP		0.16

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: rs151024633; hg19: chrX-15311379;