rs151344612

Variant names:

• chr7-151180964-C-G
• rs151344612
• NM_001142459.2:c.1079G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-151180964-C-G
• chr7-151180964-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001142459.2(ASB10):​c.1079G>C​(p.Arg360Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000709 in 1,410,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R360H) has been classified as Uncertain significance.

• 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: 4.68
• Publications: 0 publications found

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]

ASB10 Gene-Disease associations (from GenCC):

• glaucoma 1, open angle, F

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.834

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.1079G>C	p.Arg360Pro	missense_variant	Exon 3 of 6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4	c.1034G>C	p.Arg345Pro	missense_variant	Exon 3 of 6		NP_543147.2
ASB10	NM_001142460.1	c.1079G>C	p.Arg360Pro	missense_variant	Exon 3 of 5		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3	c.1079G>C	p.Arg360Pro	missense_variant	Exon 3 of 6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5	c.1079G>C	p.Arg360Pro	missense_variant	Exon 3 of 5	1		ENSP00000275838.1
ASB10	ENST00000377867.7	c.1034G>C	p.Arg345Pro	missense_variant	Exon 3 of 6	2		ENSP00000367098.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1410644 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 694426

African (AFR) AF: 0.0000308 AC: 1 AN: 32446

American (AMR) AF: 0.00 AC: 0 AN: 40468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23950

East Asian (EAS) AF: 0.00 AC: 0 AN: 38678

South Asian (SAS) AF: 0.00 AC: 0 AN: 81710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4646

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081444

Other (OTH) AF: 0.00 AC: 0 AN: 57864

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	.;.;T
Eigen	Benign	0.19
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	-0.28	N;.;N
PhyloP100		4.7
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.1	N;N;N
REVEL	Uncertain	0.47
Sift	Benign	0.10	T;T;D
Sift4G	Benign	0.070	T;T;T
Polyphen		1.0	.;D;D
Vest4		0.85
MVP		0.71
MPC		0.12
ClinPred		0.96	D
GERP RS		5.1
Varity_R		0.59
gMVP		0.78
Mutation Taster		=29/71	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs151344612; hg19: chr7-150878051;