X-15248902-G-A

Position:

• chrX-15248902-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001031739.3(ASB9):​c.602C>T​(p.Ser201Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: ASB9 NM_001031739.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58

Genes affected

ASB9 (HGNC:17184): (ankyrin repeat and SOCS box containing 9) This gene encodes a member of the ankyrin repeat and suppressor of cytokine signaling (SOCS) box protein family. Members of this family can interact with the elongin B-C adapter complex via their SOCS box domain and further complex with the cullin and ring box proteins to form E3 ubiquitin ligase complexes. They may function to mediate the substrate-recognition of the E3 ubiquitin ligases. A transcribed pseudogene of this gene has been identified on chromosome 15. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

ASB9 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.891

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB9	NM_001031739.3	c.602C>T	p.Ser201Phe	missense_variant	6/7	ENST00000380488.9	NP_001026909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB9	ENST00000380488.9	c.602C>T	p.Ser201Phe	missense_variant	6/7	1	NM_001031739.3	ENSP00000369855.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2022

The c.602C>T (p.S201F) alteration is located in exon 6 (coding exon 6) of the ASB9 gene. This alteration results from a C to T substitution at nucleotide position 602, causing the serine (S) at amino acid position 201 to be replaced by a phenylalanine (F). 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	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;.;T;.
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;.;D;D
M_CAP	Pathogenic	0.73	D
MetaRNN	Pathogenic	0.89	D;D;D;D
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.6	.;M;M;M
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-4.5	D;D;D;D
REVEL	Uncertain	0.49
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;T;D
Polyphen		1.0	.;D;D;D
Vest4		0.82
MutPred		0.63		.;Loss of disorder (P = 0.0087);Loss of disorder (P = 0.0087);Loss of disorder (P = 0.0087);
MVP		0.96
MPC		0.98
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.86
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-15267024;