rs149136882

Variant names:

• chr12-6872463-G-A
• rs149136882
• NM_032641.4:c.439C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-6872463-G-A
• chr12-6872463-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032641.4(SPSB2):​c.439C>T​(p.Pro147Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,613,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: SPSB2 NM_032641.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.14
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.027980119).

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.439C>T	p.Pro147Ser	missense	Exon 2 of 3	NP_116030.1	Q99619-1
	SPSB2	NM_001146316.2		c.439C>T	p.Pro147Ser	missense	Exon 2 of 3	NP_001139788.1	Q99619-1
	SPSB2	NM_001319670.2		c.439C>T	p.Pro147Ser	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.439C>T	p.Pro147Ser	missense	Exon 2 of 3	ENSP00000428338.1	Q99619-1
	SPSB2	ENST00000523102.5	TSL:1	c.439C>T	p.Pro147Ser	missense	Exon 2 of 3	ENSP00000430872.1	Q99619-1
	SPSB2	ENST00000519357.1	TSL:2	c.439C>T	p.Pro147Ser	missense	Exon 2 of 2	ENSP00000431037.1	Q99619-2

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000323

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000836 AC: 21 AN: 251098 AF XY: 0.0000810

Gnomad AFR exome AF: 0.00

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: 0.000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000233 AC: 340 AN: 1461654 Hom.: 0 Cov.: 32 AF XY: 0.000245 AC XY: 178 AN XY: 727168

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000301 AC: 335 AN: 1111990

Other (OTH) AF: 0.0000662 AC: 4 AN: 60388

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152218 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74364

African (AFR) AF: 0.0000724 AC: 3 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.000106

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.000218

EpiControl AF: 0.000119

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	0.082
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.85
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.1	N
PhyloP100		1.1
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.024
Sift	Benign	0.74	T
Sift4G	Benign	0.85	T
Polyphen		0.0	B
Vest4		0.25
MVP		0.072
MPC		0.23
ClinPred		0.079	T
GERP RS		1.8
Varity_R		0.17
gMVP		0.30
Mutation Taster		=97/3	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: rs149136882; hg19: chr12-6981627;