17-44172177-G-A

Variant names:

• chr17-44172177-G-A
• rs752303230
• NM_080863.5:c.433G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_080863.5(ASB16):​c.433G>A​(p.Ala145Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,612,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: ASB16 NM_080863.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0270

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.019269556).
• BP6: Variant 17-44172177-G-A is Benign according to our data. Variant chr17-44172177-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3434512.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB16	NM_080863.5	c.433G>A	p.Ala145Thr	missense_variant	Exon 2 of 5	ENST00000293414.6	NP_543139.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB16	ENST00000293414.6	c.433G>A	p.Ala145Thr	missense_variant	Exon 2 of 5	1	NM_080863.5	ENSP00000293414.1
ASB16	ENST00000589618.1	n.433G>A		non_coding_transcript_exon_variant	Exon 2 of 5	1		ENSP00000466033.1
ASB16	ENST00000591700.1	c.181G>A	p.Ala61Thr	missense_variant	Exon 3 of 3	4		ENSP00000466349.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 151858 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000180 AC: 45 AN: 250082 Hom.: 0 AF XY: 0.000155 AC XY: 21 AN XY: 135424

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000418 AC: 61 AN: 1460176 Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29 AN XY: 726496

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 151858 Hom.: 0 Cov.: 30 AF XY: 0.0000405 AC XY: 3 AN XY: 74128

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000869

ExAC AF: 0.000231 AC: 28

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 13, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.083
DANN	Benign	0.83
DEOGEN2	Benign	0.066	T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.019	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.9	.;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.74	.;N
REVEL	Benign	0.083
Sift	Benign	0.88	.;T
Sift4G	Uncertain	0.033	D;T
Polyphen		0.0040	.;B
Vest4		0.19
MutPred		0.67		.;Gain of phosphorylation at A145 (P = 0.0747);
MVP		0.092
MPC		0.30
ClinPred		0.046	T
GERP RS		-1.3
Varity_R		0.025
gMVP		0.33

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: rs752303230; hg19: chr17-42249545;