7-151176643-T-C

Variant names:

• chr7-151176643-T-C
• rs973068070
• NM_001142459.2:c.1138A>G

Variant summary

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

The NM_001142459.2(ASB10):​c.1138A>G​(p.Ile380Val) 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 1,399,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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: 7.1e-7 (0 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1855652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.1138A>G	p.Ile380Val	missense_variant	Exon 4 of 6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4	c.1093A>G	p.Ile365Val	missense_variant	Exon 4 of 6		NP_543147.2
ASB10	NM_001142460.1	c.1105-346A>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.1138A>G	p.Ile380Val	missense_variant	Exon 4 of 6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5	c.1105-346A>G		intron_variant	Intron 3 of 4	1		ENSP00000275838.1
ASB10	ENST00000377867.7	c.1093A>G	p.Ile365Val	missense_variant	Exon 4 of 6	2		ENSP00000367098.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399168 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 690036

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	.;T
Eigen	Benign	0.051
Eigen_PC	Benign	0.086
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.54	N;N
REVEL	Benign	0.26
Sift	Benign	0.069	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.91	P;P
Vest4		0.13
MutPred		0.40		.;Gain of catalytic residue at I380 (P = 0.0338);
MVP		0.38
MPC		0.10
ClinPred		0.75	D
GERP RS		4.5
Varity_R		0.10
gMVP		0.25

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: rs973068070; hg19: chr7-150873730;