NM_001142459.2:c.1132C>G

Variant names:

• chr7-151176649-G-C
• rs61628535
• NM_001142459.2:c.1132C>G

Variant summary

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

The NM_001142459.2(ASB10):​c.1132C>G​(p.Arg378Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,146 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.1132C>G	p.Arg378Gly	missense_variant	Exon 4 of 6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4	c.1087C>G	p.Arg363Gly	missense_variant	Exon 4 of 6		NP_543147.2
ASB10	NM_001142460.1	c.1105-352C>G		intron_variant	Intron 3 of 4		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3	c.1132C>G	p.Arg378Gly	missense_variant	Exon 4 of 6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5	c.1105-352C>G		intron_variant	Intron 3 of 4	1		ENSP00000275838.1
ASB10	ENST00000377867.7	c.1087C>G	p.Arg363Gly	missense_variant	Exon 4 of 6	2		ENSP00000367098.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000637 AC: 1 AN: 157036 Hom.: 0 AF XY: 0.0000120 AC XY: 1 AN XY: 83140

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: 0.0000439

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399146 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690022

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: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000371 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.083	.;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	1.7	.;L
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Uncertain	0.48
Sift	Benign	0.082	T;D
Sift4G	Benign	0.090	T;T
Polyphen		1.0	D;P
Vest4		0.64
MutPred		0.68		.;Loss of MoRF binding (P = 0.0262);
MVP		0.70
MPC		0.068
ClinPred		0.62	D
GERP RS		1.0
Varity_R		0.40
gMVP		0.51

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: rs61628535; hg19: chr7-150873736;