rs370146414

Variant names:

• chr12-6872639-A-G
• NM_032641.4:c.263T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-6872639-A-G
• chr12-6872639-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032641.4(SPSB2):​c.263T>C​(p.Leu88Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SPSB2 NM_032641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.13

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPSB2	NM_032641.4	c.263T>C	p.Leu88Pro	missense_variant	Exon 2 of 3	ENST00000524270.6	NP_116030.1
SPSB2	NM_001146316.2	c.263T>C	p.Leu88Pro	missense_variant	Exon 2 of 3		NP_001139788.1
SPSB2	NM_001319670.2	c.263T>C	p.Leu88Pro	missense_variant	Exon 1 of 2		NP_001306599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPSB2	ENST00000524270.6	c.263T>C	p.Leu88Pro	missense_variant	Exon 2 of 3	1	NM_032641.4	ENSP00000428338.1
SPSB2	ENST00000523102.5	c.263T>C	p.Leu88Pro	missense_variant	Exon 2 of 3	1		ENSP00000430872.1
SPSB2	ENST00000519357.1	c.263T>C	p.Leu88Pro	missense_variant	Exon 2 of 2	2		ENSP00000431037.1
SPSB2	ENST00000432205.5	c.*16T>C		downstream_gene_variant		3		ENSP00000428458.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459164 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725984

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	D;D;.
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.97	.;D;D
M_CAP	Uncertain	0.098	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Pathogenic	3.2	M;M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-6.0	D;D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.018	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.95
MutPred		0.63		Gain of catalytic residue at E92 (P = 0.0056);Gain of catalytic residue at E92 (P = 0.0056);Gain of catalytic residue at E92 (P = 0.0056);
MVP		0.37
MPC		1.1
ClinPred		1.0	D
GERP RS		3.8
Varity_R		0.98
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-6981803;