rs104886477

Positions:

• chr7-151181306-G-A
• chr7-151181306-G-T

Variant summary

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

The NM_001142459.2(ASB10):​c.737C>T​(p.Ala246Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A246D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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=0.07131454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASB10	NM_001142459.2	c.737C>T	p.Ala246Val	missense_variant	3/6	ENST00000420175.3
ASB10	NM_080871.4	c.692C>T	p.Ala231Val	missense_variant	3/6
ASB10	NM_001142460.1	c.737C>T	p.Ala246Val	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB10	ENST00000420175.3	c.737C>T	p.Ala246Val	missense_variant	3/6	1	NM_001142459.2	P4
ASB10	ENST00000275838.5	c.737C>T	p.Ala246Val	missense_variant	3/5	1
ASB10	ENST00000377867.7	c.692C>T	p.Ala231Val	missense_variant	3/6	2		A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Uncertain	0.99
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.071	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.52	N;.;N
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.051
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.0090, 0.0040	.;B;B
Vest4		0.18
MVP		0.39
MPC		0.050
ClinPred		0.072	T
GERP RS		3.4
Varity_R		0.057
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-150878393;