rs781804569

Variant names:

• chr12-6871291-G-C
• rs781804569
• NM_032641.4:c.693C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-6871291-G-C
• chr12-6871291-G-A

Variant summary

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

The NM_032641.4(SPSB2):​c.693C>G​(p.Ser231Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,532 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: 6.8e-7 (0 hom.)
• Consequence: SPSB2 NM_032641.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09
• Publications: 0 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.693C>G	p.Ser231Arg	missense	Exon 3 of 3	NP_116030.1	Q99619-1
	SPSB2	NM_001146316.2		c.693C>G	p.Ser231Arg	missense	Exon 3 of 3	NP_001139788.1	Q99619-1
	SPSB2	NM_001319670.2		c.693C>G	p.Ser231Arg	missense	Exon 2 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.693C>G	p.Ser231Arg	missense	Exon 3 of 3	ENSP00000428338.1	Q99619-1
	SPSB2	ENST00000523102.5	TSL:1	c.693C>G	p.Ser231Arg	missense	Exon 3 of 3	ENSP00000430872.1	Q99619-1
	SPSB2	ENST00000890095.1		c.693C>G	p.Ser231Arg	missense	Exon 2 of 2	ENSP00000560154.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461532 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727018

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111944

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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	Pathogenic	0.98
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.0077
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.29
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.53
MutPred		0.78		Gain of MoRF binding (P = 0.0316)
MVP		0.21
MPC		0.52
ClinPred		0.88	D
GERP RS		0.65
Varity_R		0.21
gMVP		0.77
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs781804569; hg19: chr12-6980455;