X-15293230-C-G

Variant names:

• chrX-15293230-C-G
• rs376376953
• NM_080873.3:c.460G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_080873.3(ASB11):​c.460G>C​(p.Gly154Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,123 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: ASB11 NM_080873.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.86

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080873.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB11	NM_080873.3	MANE Select	c.460G>C	p.Gly154Arg	missense	Exon 4 of 7	NP_543149.1	Q8WXH4-1
	ASB11	NM_001201583.2		c.409G>C	p.Gly137Arg	missense	Exon 4 of 7	NP_001188512.1	Q8WXH4-2
	ASB11	NM_001012428.2		c.397G>C	p.Gly133Arg	missense	Exon 4 of 7	NP_001012428.1	Q8WXH4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB11	ENST00000480796.6	TSL:1 MANE Select	c.460G>C	p.Gly154Arg	missense	Exon 4 of 7	ENSP00000417914.1	Q8WXH4-1
	ASB11	ENST00000380470.7	TSL:1	c.409G>C	p.Gly137Arg	missense	Exon 4 of 7	ENSP00000369837.3	Q8WXH4-2
	ASB11	ENST00000485437.2	TSL:1	n.460G>C		non_coding_transcript_exon	Exon 4 of 8	ENSP00000419385.2	F8WF31

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098123 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 363483

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.0000284 AC: 1 AN: 35190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 54126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40515

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842080

Other (OTH) AF: 0.00 AC: 0 AN: 46086

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.095	T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.69	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		2.6
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.28
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.026	D
Polyphen		0.25	B
Vest4		0.61
MutPred		0.71		Loss of ubiquitination at K156 (P = 0.1673)
MVP		0.90
MPC		0.22
ClinPred		0.89	D
GERP RS		5.3
Varity_R		0.65
gMVP		0.76
Mutation Taster		=79/21	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: rs376376953; hg19: chrX-15311352;