7-151181312-C-G

Position:

• chr7-151181312-C-G

Variant summary

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

The ENST00000420175.3(ASB10):​c.731G>C​(p.Arg244Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,872 control chromosomes in the GnomAD database, including 1 homozygotes. 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. R244H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (1 hom.)
• Consequence: ASB10 ENST00000420175.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.731G>C	p.Arg244Pro	missense_variant	3/6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4	c.686G>C	p.Arg229Pro	missense_variant	3/6		NP_543147.2
ASB10	NM_001142460.1	c.731G>C	p.Arg244Pro	missense_variant	3/5		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3	c.731G>C	p.Arg244Pro	missense_variant	3/6	1	NM_001142459.2	ENSP00000391137	P4
ASB10	ENST00000275838.5	c.731G>C	p.Arg244Pro	missense_variant	3/5	1		ENSP00000275838
ASB10	ENST00000377867.7	c.686G>C	p.Arg229Pro	missense_variant	3/6	2		ENSP00000367098	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000160 AC: 4 AN: 249470 Hom.: 1 AF XY: 0.0000222 AC XY: 3 AN XY: 135438

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460872 Hom.: 1 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 726750

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000894

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	.;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.21	N
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.91	L;.;L
MutationTaster	Benign	0.85	N;N;N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.8	D;D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.010	D;D;D
Sift4G	Benign	0.091	T;T;T
Polyphen		0.31, 0.96	.;B;D
Vest4		0.59
MVP		0.71
MPC		0.092
ClinPred		0.65	D
GERP RS		3.4
Varity_R		0.57
gMVP		0.60

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: rs104886476; hg19: chr7-150878399;