X-15289630-C-T

Variant names:

• chrX-15289630-C-T
• rs140433192
• NM_080873.3:c.529G>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.529G>A​(p.Glu177Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000381 in 1,206,072 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 0.00013 (0 hom., 6 hem., cov: 23)
  • Exomes 𝑓: 0.000029 (0 hom. 10 hem.)
• Consequence: ASB11 NM_080873.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81

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=0.18346974).
• BS2: High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB11	NM_080873.3	c.529G>A	p.Glu177Lys	missense_variant	Exon 5 of 7	ENST00000480796.6	NP_543149.1
ASB11	NM_001201583.2	c.478G>A	p.Glu160Lys	missense_variant	Exon 5 of 7		NP_001188512.1
ASB11	NM_001012428.2	c.466G>A	p.Glu156Lys	missense_variant	Exon 5 of 7		NP_001012428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB11	ENST00000480796.6	c.529G>A	p.Glu177Lys	missense_variant	Exon 5 of 7	1	NM_080873.3	ENSP00000417914.1
ASB11	ENST00000380470.7	c.478G>A	p.Glu160Lys	missense_variant	Exon 5 of 7	1		ENSP00000369837.3
ASB11	ENST00000485437.2	n.647G>A		non_coding_transcript_exon_variant	Exon 6 of 8	1		ENSP00000419385.2
ASB11	ENST00000344384.8	c.466G>A	p.Glu156Lys	missense_variant	Exon 5 of 7	5		ENSP00000343408.4

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 14 AN: 111674 Hom.: 0 Cov.: 23 AF XY: 0.000177 AC XY: 6 AN XY: 33860

Gnomad AFR AF: 0.000358

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000840

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000999 AC: 18 AN: 180140 Hom.: 0 AF XY: 0.0000773 AC XY: 5 AN XY: 64720

Gnomad AFR exome AF: 0.000611

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000660

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000224

GnomAD4 exome AF: 0.0000292 AC: 32 AN: 1094398 Hom.: 0 Cov.: 29 AF XY: 0.0000278 AC XY: 10 AN XY: 359942

Gnomad4 AFR exome AF: 0.000152

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000464

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000305

GnomAD4 genome AF: 0.000125 AC: 14 AN: 111674 Hom.: 0 Cov.: 23 AF XY: 0.000177 AC XY: 6 AN XY: 33860

Gnomad4 AFR AF: 0.000358

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000840

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000189

ESP6500AA AF: 0.00156 AC: 6

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000988 AC: 12

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.529G>A (p.E177K) alteration is located in exon 5 (coding exon 5) of the ASB11 gene. This alteration results from a G to A substitution at nucleotide position 529, causing the glutamic acid (E) at amino acid position 177 to be replaced by a lysine (K). 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	0.15
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	.;.;T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D;T;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.2	.;.;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.075	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		1.0	.;.;D
Vest4		0.49
MVP		0.82
MPC		0.092
ClinPred		0.046	T
GERP RS		4.7
Varity_R		0.43
gMVP		0.49

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: rs140433192; hg19: chrX-15307752;