7-123624628-G-A

Variant names:

• chr7-123624628-G-A
• rs996815686
• NM_001290258.2:c.511G>A

Variant summary

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

The NM_001290258.2(ASB15):​c.511G>A​(p.Asp171Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ASB15 NM_001290258.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96

Genes affected

ASB15 (HGNC:19767): (ankyrin repeat and SOCS box containing 15) This gene encodes a member of the suppressor of cytokine signaling box superfamily. The proteins in this superfamily participate in the ubiquitin-proteasome system for the degradation of proteins in the cell cycle and signal transduction pathways. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ASB15-AS1 (HGNC:40904): (ASB15 antisense RNA 1)

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=0.085600555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB15	NM_001290258.2	c.511G>A	p.Asp171Asn	missense_variant	Exon 8 of 12	ENST00000451215.6	NP_001277187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB15	ENST00000451215.6	c.511G>A	p.Asp171Asn	missense_variant	Exon 8 of 12	2	NM_001290258.2	ENSP00000416433.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461758 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727204

Gnomad4 AFR exome AF: 0.0000597

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.511G>A (p.D171N) alteration is located in exon 6 (coding exon 5) of the ASB15 gene. This alteration results from a G to A substitution at nucleotide position 511, causing the aspartic acid (D) at amino acid position 171 to be replaced by an asparagine (N). 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	0.074
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	20
DANN	Benign	0.66
DEOGEN2	Benign	0.0065	T;T;T;.;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.84	.;.;.;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.086	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.82	N;N;N;.;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.9	N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	B;B;B;.;B
Vest4		0.16
MutPred		0.55		Gain of MoRF binding (P = 0.0342);Gain of MoRF binding (P = 0.0342);Gain of MoRF binding (P = 0.0342);Gain of MoRF binding (P = 0.0342);Gain of MoRF binding (P = 0.0342);
MVP		0.53
MPC		0.13
ClinPred		0.31	T
GERP RS		4.8
Varity_R		0.065
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: rs996815686; hg19: chr7-123264682; COSMIC: COSV104994854; COSMIC: COSV104994854;