17-44171043-T-C

Variant names:

• chr17-44171043-T-C
• NM_080863.5:c.254T>C

Variant summary

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

The NM_080863.5(ASB16):​c.254T>C​(p.Met85Thr) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ASB16 NM_080863.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.48

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24856672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB16	NM_080863.5	c.254T>C	p.Met85Thr	missense_variant	Exon 1 of 5	ENST00000293414.6	NP_543139.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB16	ENST00000293414.6	c.254T>C	p.Met85Thr	missense_variant	Exon 1 of 5	1	NM_080863.5	ENSP00000293414.1
ASB16	ENST00000589618.1	n.254T>C		non_coding_transcript_exon_variant	Exon 1 of 5	1		ENSP00000466033.1
ASB16	ENST00000591700.1	c.2T>C	p.Met1?	start_lost	Exon 2 of 3	4		ENSP00000466349.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.254T>C (p.M85T) alteration is located in exon 1 (coding exon 1) of the ASB16 gene. This alteration results from a T to C substitution at nucleotide position 254, causing the methionine (M) at amino acid position 85 to be replaced by a threonine (T). 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	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.045	T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.90	D;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.060	.;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.3	.;N
REVEL	Benign	0.19
Sift	Uncertain	0.026	.;D
Sift4G	Uncertain	0.044	D;T
Polyphen		0.19	.;B
Vest4		0.54
MutPred		0.41		.;Loss of catalytic residue at M85 (P = 0.0077);
MVP		0.40
MPC		0.38
ClinPred		0.82	D
GERP RS		4.3
Varity_R		0.34
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr17-42248411;