17-44172061-C-T

Variant names:

• chr17-44172061-C-T
• rs778143490
• NM_080863.5:c.317C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080863.5(ASB16):​c.317C>T​(p.Thr106Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T106N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ASB16 NM_080863.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203
• Publications: 0 publications found

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]

ASB16-AS1 (HGNC:25442): (ASB16 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18341401).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080863.5. 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
	ASB16	NM_080863.5	MANE Select	c.317C>T	p.Thr106Ile	missense	Exon 2 of 5	NP_543139.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB16	ENST00000293414.6	TSL:1 MANE Select	c.317C>T	p.Thr106Ile	missense	Exon 2 of 5	ENSP00000293414.1	Q96NS5
	ASB16	ENST00000589618.1	TSL:1	n.317C>T		non_coding_transcript_exon	Exon 2 of 5	ENSP00000466033.1	K7ELE0
	ASB16	ENST00000591700.1	TSL:4	c.65C>T	p.Thr22Ile	missense	Exon 3 of 3	ENSP00000466349.1	K7EM41

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460154 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726430

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111874

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.0097
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.045	N
PhyloP100		-0.20
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.13
Sift	Benign	0.091	T
Sift4G	Benign	0.088	T
Polyphen		0.17	B
Vest4		0.30
MutPred		0.40		Loss of ubiquitination at K110 (P = 0.0516)
MVP		0.50
MPC		0.35
ClinPred		0.56	D
GERP RS		5.5
Varity_R		0.27
gMVP		0.57
Mutation Taster		=82/18	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: rs778143490; hg19: chr17-42249429;