chrX-64224379-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_130388.4(ASB12):​c.913G>C​(p.Asp305His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Consequence

ASB12
NM_130388.4 missense

Scores

4
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25839996).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASB12NM_130388.4 linkc.913G>C p.Asp305His missense_variant Exon 3 of 3 ENST00000362002.3 NP_569059.3 Q8WXK4-2
LOC112268307XM_047442705.1 linkc.125+17339C>G intron_variant Intron 2 of 4 XP_047298661.1
LOC112268307XM_047442706.1 linkc.125+17339C>G intron_variant Intron 2 of 3 XP_047298662.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASB12ENST00000362002.3 linkc.913G>C p.Asp305His missense_variant Exon 3 of 3 2 NM_130388.4 ENSP00000355195.2 Q8WXK4-2
ENSG00000287370ENST00000671386.1 linkn.171-9012C>G intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 28, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.913G>C (p.D305H) alteration is located in exon 3 (coding exon 2) of the ASB12 gene. This alteration results from a G to C substitution at nucleotide position 913, causing the aspartic acid (D) at amino acid position 305 to be replaced by a histidine (H). 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
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
23
DANN
Uncertain
0.99
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.64
T
M_CAP
Benign
0.0079
T
MetaRNN
Benign
0.26
T
MetaSVM
Benign
-0.94
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.18
Sift
Uncertain
0.029
D
Sift4G
Uncertain
0.038
D
Vest4
0.19
MVP
0.45
MPC
0.010
ClinPred
0.89
D
GERP RS
3.7
gMVP
0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-63444259; API