rs575382169

Variant names:

• chr4-176222411-C-T
• rs575382169
• NM_080874.4:c.286G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-176222411-C-T
• chr4-176222411-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080874.4(ASB5):​c.286G>A​(p.Val96Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ASB5 NM_080874.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.03
• Publications: 1 publications found

Genes affected

ASB5 (HGNC:17180): (ankyrin repeat and SOCS box containing 5) 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 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. Multiple alternatively spliced transcript variants have been described for this gene but their full length sequences are not known. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34240967).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080874.4. 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
	ASB5	NM_080874.4	MANE Select	c.286G>A	p.Val96Ile	missense	Exon 3 of 7	NP_543150.1	Q8WWX0-1
	ASB5	NM_001410863.1		c.151G>A	p.Val51Ile	missense	Exon 3 of 7	NP_001397792.1	A0A5F9ZHS2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB5	ENST00000296525.7	TSL:1 MANE Select	c.286G>A	p.Val96Ile	missense	Exon 3 of 7	ENSP00000296525.3	Q8WWX0-1
	ASB5	ENST00000855722.1		c.286G>A	p.Val96Ile	missense	Exon 4 of 8	ENSP00000525781.1
	ASB5	ENST00000855723.1		c.286G>A	p.Val96Ile	missense	Exon 6 of 10	ENSP00000525782.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250178 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459740 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726238

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.00 AC: 0 AN: 44446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 85926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110710

Other (OTH) AF: 0.00 AC: 0 AN: 60316

GnomAD4 genome Cov.: 33

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	0.11
BayesDel_addAF	Benign	0.0068	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.77	N
PhyloP100		7.0
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.15
Sift	Uncertain	0.025	D
Sift4G	Benign	0.29	T
Polyphen		0.88	P
Vest4		0.51
MutPred		0.49		Gain of catalytic residue at L101 (P = 0.023)
MVP		0.36
MPC		0.30
ClinPred		0.89	D
GERP RS		5.4
Varity_R		0.13
gMVP		0.54
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs575382169; hg19: chr4-177143562;