chr7-151180947-G-C

Position:

• chr7-151180947-G-C

Variant summary

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

The NM_001142459.2(ASB10):​c.1096C>G​(p.Leu366Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,258 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L366F) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09

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/exons	MANE	UniProt
ASB10	NM_001142459.2	c.1096C>G	p.Leu366Val	missense_variant	3/6	ENST00000420175.3
ASB10	NM_080871.4	c.1051C>G	p.Leu351Val	missense_variant	3/6
ASB10	NM_001142460.1	c.1096C>G	p.Leu366Val	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB10	ENST00000420175.3	c.1096C>G	p.Leu366Val	missense_variant	3/6	1	NM_001142459.2	P4
ASB10	ENST00000275838.5	c.1096C>G	p.Leu366Val	missense_variant	3/5	1
ASB10	ENST00000377867.7	c.1051C>G	p.Leu351Val	missense_variant	3/6	2		A1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152258 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152258 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74390

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	.;.;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T;D;D
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.3	M;.;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.79	N;N;N
REVEL	Benign	0.26
Sift	Uncertain	0.014	D;D;D
Sift4G	Uncertain	0.021	D;D;D
Polyphen		1.0, 1.0	.;D;D
Vest4		0.62
MVP		0.56
MPC		0.29
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.27
gMVP		0.43

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: rs104886485; hg19: chr7-150878034;