9-129638348-G-C

Position:

• chr9-129638348-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000277458.5(ASB6):​c.708C>G​(p.Asn236Lys) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASB6 ENST00000277458.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0370

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

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=0.13010761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB6	NM_017873.4	c.708C>G	p.Asn236Lys	missense_variant	6/6	ENST00000277458.5	NP_060343.1
ASB6	NM_001202403.2	c.621C>G	p.Asn207Lys	missense_variant	5/5		NP_001189332.1
ASB6	NM_177999.3	c.*5C>G		3_prime_UTR_variant	5/5		NP_821066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB6	ENST00000277458.5	c.708C>G	p.Asn236Lys	missense_variant	6/6	1	NM_017873.4	ENSP00000277458.4
ASB6	ENST00000450050.6	c.621C>G	p.Asn207Lys	missense_variant	5/5	1		ENSP00000416172.3
ASB6	ENST00000277459.8	c.*5C>G		3_prime_UTR_variant	5/5	1		ENSP00000277459.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.708C>G (p.N236K) alteration is located in exon 6 (coding exon 6) of the ASB6 gene. This alteration results from a C to G substitution at nucleotide position 708, causing the asparagine (N) at amino acid position 236 to be replaced by a lysine (K). 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
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.058	T;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.2	.;L
MutationTaster	Benign	0.82	D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.4	.;N
REVEL	Benign	0.047
Sift	Benign	0.46	.;T
Sift4G	Benign	0.83	T;T
Polyphen		0.020	.;B
Vest4		0.35
MutPred		0.58		.;Gain of methylation at N236 (P = 0.0124);
MVP		0.43
MPC		0.41
ClinPred		0.14	T
GERP RS		2.5
Varity_R		0.10
gMVP		0.34

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: chr9-132400627;