1-75919031-G-C

Position:

• chr1-75919031-G-C

Variant summary

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

The NM_080868.3(ASB17):​c.809C>G​(p.Thr270Ser) 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 1,460,230 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ASB17 NM_080868.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.651

Genes affected

ASB17 (HGNC:19769): (ankyrin repeat and SOCS box containing 17) Predicted to be involved in intracellular signal transduction and protein ubiquitination. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ASB17 (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=0.08741203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB17	NM_080868.3	c.809C>G	p.Thr270Ser	missense_variant	3/3	ENST00000284142.7	NP_543144.1
ASB17	XM_047445206.1	c.575C>G	p.Thr192Ser	missense_variant	3/3		XP_047301162.1
ASB17	NR_026546.3	n.860C>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB17	ENST00000284142.7	c.809C>G	p.Thr270Ser	missense_variant	3/3	1	NM_080868.3	ENSP00000284142.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460230 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726606

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

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

Jan 19, 2022

The c.809C>G (p.T270S) alteration is located in exon 3 (coding exon 3) of the ASB17 gene. This alteration results from a C to G substitution at nucleotide position 809, causing the threonine (T) at amino acid position 270 to be replaced by a serine (S). 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	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.53	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.012
Sift	Benign	0.15	T
Sift4G	Benign	0.20	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.41		Loss of catalytic residue at T270 (P = 0.0735);
MVP		0.32
MPC		0.022
ClinPred		0.13	T
GERP RS		1.4
Varity_R		0.036
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-76384716;