rs104886479

chr7-151181135-C-Achr7-151181135-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001142459.2(ASB10):c.908G>T(p.Arg303Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,459,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R303H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64

Genes affected

ASB10 (HGNC:17185): (ankyrin repeat and SOCS box containing 10) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. The SOCS box serves to couple suppressor of cytokine signaling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22184771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASB10	NM_001142459.2	c.908G>T	p.Arg303Leu	missense_variant	3/6	ENST00000420175.3
ASB10	NM_080871.4	c.863G>T	p.Arg288Leu	missense_variant	3/6
ASB10	NM_001142460.1	c.908G>T	p.Arg303Leu	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB10	ENST00000420175.3	c.908G>T	p.Arg303Leu	missense_variant	3/6	1	NM_001142459.2	P4
ASB10	ENST00000275838.5	c.908G>T	p.Arg303Leu	missense_variant	3/5	1
ASB10	ENST00000377867.7	c.863G>T	p.Arg288Leu	missense_variant	3/6	2		A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000815 AC: 2 AN: 245344 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 133796

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000183

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1459260 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 725786

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: 0.00000810

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.31
Cadd	Uncertain	23
Dann	Uncertain	0.99
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.053
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.85	D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.44	N;.;N
MutationTaster	Benign	0.91	D;D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.21
Sift	Benign	0.054	T;T;D
Sift4G	Uncertain	0.054	T;D;T
Polyphen		0.018, 0.098	.;B;B
Vest4		0.28
MVP		0.61
MPC		0.064
ClinPred		0.80	D
GERP RS		4.5
Varity_R		0.23
gMVP		0.41

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: rs104886479; hg19: chr7-150878222;