12-6872492-C-T

Variant names:

• chr12-6872492-C-T
• rs143198615
• NM_032641.4:c.410G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032641.4(SPSB2):​c.410G>A​(p.Arg137Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,460,636 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: SPSB2 NM_032641.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.94
• Publications: 1 publications found

Genes affected

SPSB2 (HGNC:29522): (splA/ryanodine receptor domain and SOCS box containing 2) This gene encodes a member of a subfamily of proteins containing a central SPRY (repeats in splA and RyR) domain and a C-terminal suppressor of cytokine signaling (SOCS) box. This protein plays a role in cell signaling. This gene is present in a gene-rich cluster on chromosome 12p13 in the vicinity of the CD4 antigen and triosephosphate isomerase genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032641.4. 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
	SPSB2	NM_032641.4	MANE Select	c.410G>A	p.Arg137Gln	missense	Exon 2 of 3	NP_116030.1	Q99619-1
	SPSB2	NM_001146316.2		c.410G>A	p.Arg137Gln	missense	Exon 2 of 3	NP_001139788.1	Q99619-1
	SPSB2	NM_001319670.2		c.410G>A	p.Arg137Gln	missense	Exon 1 of 2	NP_001306599.1	Q99619-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPSB2	ENST00000524270.6	TSL:1 MANE Select	c.410G>A	p.Arg137Gln	missense	Exon 2 of 3	ENSP00000428338.1	Q99619-1
	SPSB2	ENST00000523102.5	TSL:1	c.410G>A	p.Arg137Gln	missense	Exon 2 of 3	ENSP00000430872.1	Q99619-1
	SPSB2	ENST00000519357.1	TSL:2	c.410G>A	p.Arg137Gln	missense	Exon 2 of 2	ENSP00000431037.1	Q99619-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000800 AC: 2 AN: 250110 AF XY: 0.00

Gnomad AFR exome AF: 0.0000618

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: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1460636 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 726632

African (AFR) AF: 0.000119 AC: 4 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111760

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.14
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	0.018
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.70	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.9
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.21
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.058	T
Polyphen		0.91	P
Vest4		0.75
MVP		0.15
MPC		0.83
ClinPred		0.94	D
GERP RS		3.0
Varity_R		0.44
gMVP		0.37
Mutation Taster		=81/19	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: rs143198615; hg19: chr12-6981656; COSMIC: COSV105063970; COSMIC: COSV105063970;