2-53693919-C-T

Variant names:

• chr2-53693919-C-T
• rs11553661
• NM_016115.5:c.1334G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016115.5(ASB3):​c.1334G>A​(p.Arg445His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,474 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: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: ASB3 NM_016115.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36
• Publications: 1 publications found

Genes affected

ASB3 (HGNC:16013): (ankyrin repeat and SOCS box containing 3) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jan 2011]

GPR75-ASB3 (HGNC:40043): (GPR75-ASB3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring GPR75 (G protein-coupled receptor 75) and ASB3 (ankyrin repeat and SOCS box containing 3) on chromosome 2. The transcript includes exons from both GPR75 and ASB3 and translation initiates in the 5' non-coding exon of GPR75. The resulting protein has a novel N-terminus but is otherwise identical to that encoded by ASB3.[provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07725236).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016115.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB3	NM_016115.5	MANE Select	c.1334G>A	p.Arg445His	missense	Exon 9 of 10	NP_057199.1	Q9Y575-1
	GPR75-ASB3	NM_001164165.2		c.1448G>A	p.Arg483His	missense	Exon 9 of 10	NP_001157637.1
	ASB3	NM_001201965.2		c.1115G>A	p.Arg372His	missense	Exon 8 of 9	NP_001188894.1	Q9Y575-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB3	ENST00000263634.8	TSL:1 MANE Select	c.1334G>A	p.Arg445His	missense	Exon 9 of 10	ENSP00000263634.2	Q9Y575-1
	ASB3	ENST00000406625.6	TSL:2	c.1334G>A	p.Arg445His	missense	Exon 9 of 10	ENSP00000385085.4	Q9Y575-1
	ASB3	ENST00000893612.1		c.1334G>A	p.Arg445His	missense	Exon 9 of 10	ENSP00000563671.1

Frequencies

GnomAD3 genomes AF: 0.000178 AC: 27 AN: 152080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000403 AC: 10 AN: 248072 AF XY: 0.00000745

Gnomad AFR exome AF: 0.000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000274 AC: 40 AN: 1461276 Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15 AN XY: 726948

African (AFR) AF: 0.000568 AC: 19 AN: 33448

American (AMR) AF: 0.0000224 AC: 1 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111596

Other (OTH) AF: 0.0000331 AC: 2 AN: 60362

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74426

African (AFR) AF: 0.000530 AC: 22 AN: 41546

American (AMR) AF: 0.000196 AC: 3 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.0000795 Hom.: 0

Bravo AF: 0.000272

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000577 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.073
Sift	Benign	0.21	T
Sift4G	Benign	0.10	T
Polyphen		0.0020	B
Vest4		0.18
MVP		0.50
MPC		0.064
ClinPred		0.062	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.040
gMVP		0.37
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs11553661; hg19: chr2-53921056;