chrX-64224430-C-T

Variant names:

• chrX-64224430-C-T
• rs748815216
• NM_130388.4:c.862G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_130388.4(ASB12):​c.862G>A​(p.Val288Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000331 in 1,208,171 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V288A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000036 (0 hom. 12 hem.)
• Consequence: ASB12 NM_130388.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.473
• Publications: 1 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.028640598).
• BP6: Variant X-64224430-C-T is Benign according to our data. Variant chrX-64224430-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2514029.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 12 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.862G>A	p.Val288Ile	missense	Exon 3 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.862G>A	p.Val288Ile	missense	Exon 3 of 3	ENSP00000355195.2	Q8WXK4-2
	ENSG00000287370	ENST00000671386.1		n.171-8961C>T		intron	N/A
	ENSG00000287370	ENST00000747759.1		n.229+17390C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000900 AC: 1 AN: 111146 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000328

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000383 AC: 7 AN: 182579 AF XY: 0.0000298

Gnomad AFR exome AF: 0.0000762

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000246

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000356 AC: 39 AN: 1096973 Hom.: 0 Cov.: 30 AF XY: 0.0000331 AC XY: 12 AN XY: 362365

African (AFR) AF: 0.0000379 AC: 1 AN: 26377

American (AMR) AF: 0.00 AC: 0 AN: 35185

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19378

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30195

South Asian (SAS) AF: 0.0000740 AC: 4 AN: 54056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4127

European-Non Finnish (NFE) AF: 0.0000369 AC: 31 AN: 841100

Other (OTH) AF: 0.0000434 AC: 2 AN: 46057

GnomAD4 genome AF: 0.00000899 AC: 1 AN: 111198 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33422

African (AFR) AF: 0.0000327 AC: 1 AN: 30555

American (AMR) AF: 0.00 AC: 0 AN: 10538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3495

South Asian (SAS) AF: 0.00 AC: 0 AN: 2577

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5975

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52980

Other (OTH) AF: 0.00 AC: 0 AN: 1524

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.054
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.6
DANN	Benign	0.20
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.47
PROVEAN	Benign	0.32	N
REVEL	Benign	0.030
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.037
MVP		0.29
MPC		0.0092
ClinPred		0.0055	T
GERP RS		2.6
gMVP		0.12
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs748815216; hg19: chrX-63444310; COSMIC: COSV62857329;