17-44172126-C-G

Position:

• chr17-44172126-C-G

Variant summary

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

The ENST00000293414.6(ASB16):​c.382C>G​(p.Arg128Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,414 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ASB16 ENST00000293414.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31

Genes affected

ASB16 (HGNC:19768): (ankyrin repeat and SOCS box containing 16) 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, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB16	NM_080863.5	c.382C>G	p.Arg128Gly	missense_variant	2/5	ENST00000293414.6	NP_543139.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB16	ENST00000293414.6	c.382C>G	p.Arg128Gly	missense_variant	2/5	1	NM_080863.5	ENSP00000293414	P1
ASB16	ENST00000589618.1	c.382C>G	p.Arg128Gly	missense_variant, NMD_transcript_variant	2/5	1		ENSP00000466033
ASB16	ENST00000591700.1	c.130C>G	p.Arg44Gly	missense_variant	3/3	4		ENSP00000466349

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459414 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

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 17, 2021

The c.382C>G (p.R128G) alteration is located in exon 2 (coding exon 2) of the ASB16 gene. This alteration results from a C to G substitution at nucleotide position 382, causing the arginine (R) at amino acid position 128 to be replaced by a glycine (G). 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	0.16
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.3	.;M
MutationTaster	Benign	0.79	D
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-5.0	.;D
REVEL	Benign	0.28
Sift	Uncertain	0.0060	.;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.95	.;P
Vest4		0.56
MutPred		0.48		.;Loss of MoRF binding (P = 0.0109);
MVP		0.79
MPC		1.0
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.49
gMVP		0.71

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: rs747471011; hg19: chr17-42249494;