X-64224438-C-A

Variant names:

• chrX-64224438-C-A
• NM_130388.4:c.854G>T

Variant summary

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

The NM_130388.4(ASB12):​c.854G>T​(p.Arg285Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R285C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: ASB12 NM_130388.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.59

Genes affected

ASB12 (HGNC:19763): (ankyrin repeat and SOCS box containing 12) 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 a 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. [provided by RefSeq, Jan 2011]

LOC112268307 (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, 0.88

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB12	NM_130388.4	c.854G>T	p.Arg285Leu	missense_variant	Exon 3 of 3	ENST00000362002.3	NP_569059.3
LOC112268307	XM_047442705.1	c.125+17398C>A		intron_variant	Intron 2 of 4		XP_047298661.1
LOC112268307	XM_047442706.1	c.125+17398C>A		intron_variant	Intron 2 of 3		XP_047298662.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB12	ENST00000362002.3	c.854G>T	p.Arg285Leu	missense_variant	Exon 3 of 3	2	NM_130388.4	ENSP00000355195.2
ENSG00000287370	ENST00000671386.1	n.171-8953C>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	23
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.30	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.85
MVP		0.30
MPC		0.050
ClinPred		1.0	D
GERP RS		1.9
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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-63444318;