15-100612310-A-C

Variant names:

• chr15-100612310-A-C
• rs1189636861
• NM_198243.3:c.94A>C

Variant summary

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

The NM_198243.3(ASB7):​c.94A>C​(p.Lys32Gln) variant causes a missense change. 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASB7 NM_198243.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.93

Genes affected

ASB7 (HGNC:17182): (ankyrin repeat and SOCS box containing 7) The protein encoded by this gene belongs to a family of ankyrin repeat proteins that, along with four other protein families, contains a C-terminal SOCS box motif. Growing evidence suggests that the SOCS box acts as a bridge between specific substrate-binding domains and the more generic proteins that comprise a large family of E3 ubiquitin protein ligases. In this way, SOCS box containing proteins may regulate protein turnover by targeting proteins for polyubiquination and, therefore, for proteasome-mediated degradation. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 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=0.23861477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB7	NM_198243.3	c.94A>C	p.Lys32Gln	missense_variant	Exon 4 of 6	ENST00000332783.12	NP_937886.1
ASB7	NM_024708.4	c.94A>C	p.Lys32Gln	missense_variant	Exon 4 of 5		NP_078984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB7	ENST00000332783.12	c.94A>C	p.Lys32Gln	missense_variant	Exon 4 of 6	1	NM_198243.3	ENSP00000328327.8
ASB7	ENST00000343276.4	c.94A>C	p.Lys32Gln	missense_variant	Exon 4 of 5	1		ENSP00000339819.4
ASB7	ENST00000558747.5	c.94A>C	p.Lys32Gln	missense_variant	Exon 4 of 5	5		ENSP00000453626.1
ASB7	ENST00000561192.1	n.427A>C		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.94A>C (p.K32Q) alteration is located in exon 4 (coding exon 1) of the ASB7 gene. This alteration results from a A to C substitution at nucleotide position 94, causing the lysine (K) at amino acid position 32 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.040	T;T;.
Eigen	Benign	0.000037
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.32	N;.;N
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	0.54	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.60	T;T;T
Sift4G	Benign	0.61	T;T;T
Polyphen		0.059	B;.;B
Vest4		0.42
MutPred		0.46		Loss of MoRF binding (P = 0.099);Loss of MoRF binding (P = 0.099);Loss of MoRF binding (P = 0.099);
MVP		0.59
MPC		1.2
ClinPred		0.50	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.088
gMVP		0.80

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: rs1189636861; hg19: chr15-101152515;