chr2-238444616-G-C

Position:

• chr2-238444616-G-C

Variant summary

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

The NM_001040445.3(ASB1):​c.769G>C​(p.Val257Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASB1 NM_001040445.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.34

Genes affected

ASB1 (HGNC:16011): (ankyrin repeat and SOCS box containing 1) The protein encoded by this gene contains an 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, targeting them for ubiquitination and degradation. [provided by RefSeq, Aug 2016]

ASB1 (HGNC:):

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=0.11070058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB1	NM_001040445.3	c.769G>C	p.Val257Leu	missense_variant	4/5	ENST00000264607.9	NP_001035535.1
ASB1	NM_001330196.2	c.466G>C	p.Val156Leu	missense_variant	3/4		NP_001317125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB1	ENST00000264607.9	c.769G>C	p.Val257Leu	missense_variant	4/5	1	NM_001040445.3	ENSP00000264607.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Aug 05, 2024

The c.769G>C (p.V257L) alteration is located in exon 4 (coding exon 4) of the ASB1 gene. This alteration results from a G to C substitution at nucleotide position 769, causing the valine (V) at amino acid position 257 to be replaced by a leucine (L). 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	0.22
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.018
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.67	N;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.31	N;N
REVEL	Benign	0.075
Sift	Benign	0.19	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.0020	B;.
Vest4		0.13
MutPred		0.48		Loss of catalytic residue at V257 (P = 0.0308);.;
MVP		0.54
MPC		0.47
ClinPred		0.33	T
GERP RS		5.9
Varity_R		0.030
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs1702142684; hg19: chr2-239353257;