chrX-64225208-C-T

Variant names:

• chrX-64225208-C-T
• rs200811316
• NM_130388.4:c.443G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_130388.4(ASB12):​c.443G>A​(p.Arg148His) variant causes a missense change. The variant allele was found at a frequency of 0.0000446 in 1,209,929 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R148G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 2 hem., cov: 22)
  • Exomes 𝑓: 0.000046 (0 hom. 11 hem.)
• Consequence: ASB12 NM_130388.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.54
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13092855).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130388.4. 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
	ASB12	NM_130388.4	MANE Select	c.443G>A	p.Arg148His	missense	Exon 2 of 3	NP_569059.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB12	ENST00000362002.3	TSL:2 MANE Select	c.443G>A	p.Arg148His	missense	Exon 2 of 3	ENSP00000355195.2	Q8WXK4-2
	ENSG00000287370	ENST00000671386.1		n.171-8183C>T		intron	N/A
	ENSG00000287370	ENST00000747759.1		n.229+18168C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 3 AN: 111846 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000564

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000713 AC: 13 AN: 182403 AF XY: 0.0000149

Gnomad AFR exome AF: 0.000153

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000464 AC: 51 AN: 1098027 Hom.: 0 Cov.: 32 AF XY: 0.0000303 AC XY: 11 AN XY: 363389

African (AFR) AF: 0.000189 AC: 5 AN: 26398

American (AMR) AF: 0.0000284 AC: 1 AN: 35193

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19380

East Asian (EAS) AF: 0.00 AC: 0 AN: 30200

South Asian (SAS) AF: 0.000148 AC: 8 AN: 54063

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: 0.0000404 AC: 34 AN: 842047

Other (OTH) AF: 0.0000651 AC: 3 AN: 46095

GnomAD4 genome AF: 0.0000268 AC: 3 AN: 111902 Hom.: 0 Cov.: 22 AF XY: 0.0000587 AC XY: 2 AN XY: 34082

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30782

American (AMR) AF: 0.00 AC: 0 AN: 10585

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3530

South Asian (SAS) AF: 0.00 AC: 0 AN: 2636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6115

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0000564 AC: 3 AN: 53188

Other (OTH) AF: 0.00 AC: 0 AN: 1512

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000356 Hom.: 2

Bravo AF: 0.0000453

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.74	T
PhyloP100		5.5
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.24
Sift	Uncertain	0.029	D
Sift4G	Benign	0.15	T
Vest4		0.26
MVP		0.58
MPC		0.014
ClinPred		0.17	T
GERP RS		3.1
gMVP		0.59
Mutation Taster		=93/7	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: rs200811316; hg19: chrX-63445088;