chr7-151176251-G-A

Variant names:

• chr7-151176251-G-A
• rs566879250
• NM_001142459.2:c.1265C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001142459.2(ASB10):​c.1265C>T​(p.Pro422Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.79

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.857

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.1265C>T	p.Pro422Leu	missense_variant	Exon 5 of 6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4	c.1220C>T	p.Pro407Leu	missense_variant	Exon 5 of 6		NP_543147.2
ASB10	NM_001142460.1	c.1151C>T	p.Pro384Leu	missense_variant	Exon 4 of 5		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3	c.1265C>T	p.Pro422Leu	missense_variant	Exon 5 of 6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5	c.1151C>T	p.Pro384Leu	missense_variant	Exon 4 of 5	1		ENSP00000275838.1
ASB10	ENST00000377867.7	c.1220C>T	p.Pro407Leu	missense_variant	Exon 5 of 6	2		ENSP00000367098.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000447 AC: 1 AN: 223810 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 121834

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: 0.00000988

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1435386 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 712156

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: 9.09e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000434 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	.;.;T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.075	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Pathogenic	3.2	.;.;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-6.9	D;D;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.012	D;D;D
Sift4G	Benign	0.19	T;T;T
Polyphen		1.0, 1.0	.;D;D
Vest4		0.89
MVP		0.68
MPC		0.33
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.83
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs566879250; hg19: chr7-150873338;