chr9-129637813-C-T

Variant names:

• chr9-129637813-C-T
• rs1463550093
• NM_017873.4:c.1243G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017873.4(ASB6):​c.1243G>A​(p.Gly415Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,362,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: ASB6 NM_017873.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0680
• Publications: 0 publications found

Genes affected

ASB6 (HGNC:17181): (ankyrin repeat and SOCS box containing 6) The protein encoded by this gene belongs to a family of ankyrin repeat proteins that, along with four other protein families, contain a C-terminal SOCS box motif. Growing evidence suggests that the SOCS box, similar to the F-box, acts as a bridge between specific substrate-binding domains and the more generic proteins that comprise a large family of E3 ubiquitin protein ligases. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04995209).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017873.4. 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
	ASB6	NM_017873.4	MANE Select	c.1243G>A	p.Gly415Ser	missense	Exon 6 of 6	NP_060343.1	Q9NWX5-1
	ASB6	NM_001202403.2		c.1156G>A	p.Gly386Ser	missense	Exon 5 of 5	NP_001189332.1	F6TX30
	ASB6	NM_177999.3		c.*540G>A		3_prime_UTR	Exon 5 of 5	NP_821066.1	Q9NWX5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB6	ENST00000277458.5	TSL:1 MANE Select	c.1243G>A	p.Gly415Ser	missense	Exon 6 of 6	ENSP00000277458.4	Q9NWX5-1
	ASB6	ENST00000450050.6	TSL:1	c.1156G>A	p.Gly386Ser	missense	Exon 5 of 5	ENSP00000416172.3	F6TX30
	ASB6	ENST00000277459.8	TSL:1	c.*540G>A		3_prime_UTR	Exon 5 of 5	ENSP00000277459.4	Q9NWX5-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000565 AC: 1 AN: 176926 AF XY: 0.0000108

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: 0.0000116

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.34e-7 AC: 1 AN: 1362248 Hom.: 0 Cov.: 29 AF XY: 0.00000150 AC XY: 1 AN XY: 666526

African (AFR) AF: 0.0000332 AC: 1 AN: 30164

American (AMR) AF: 0.00 AC: 0 AN: 28836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19870

East Asian (EAS) AF: 0.00 AC: 0 AN: 38694

South Asian (SAS) AF: 0.00 AC: 0 AN: 70082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5276

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063932

Other (OTH) AF: 0.00 AC: 0 AN: 55980

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.066
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	2.0
DANN	Benign	0.82
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.068
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.059
Sift	Benign	0.31	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.22		Loss of glycosylation at S414 (P = 0.0384)
MVP		0.49
MPC		0.34
ClinPred		0.047	T
GERP RS		-0.69
Varity_R		0.057
gMVP		0.36
Mutation Taster		=96/4	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: rs1463550093; hg19: chr9-132400092;