rs200625865

Variant names:

• chr12-6871251-C-A
• rs200625865
• NM_032641.4:c.733G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-6871251-C-A
• chr12-6871251-C-G
• chr12-6871251-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032641.4(SPSB2):​c.733G>T​(p.Gly245Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SPSB2 NM_032641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22743312).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPSB2	NM_032641.4	c.733G>T	p.Gly245Cys	missense_variant	Exon 3 of 3	ENST00000524270.6	NP_116030.1
SPSB2	NM_001146316.2	c.733G>T	p.Gly245Cys	missense_variant	Exon 3 of 3		NP_001139788.1
SPSB2	NM_001319670.2	c.733G>T	p.Gly245Cys	missense_variant	Exon 2 of 2		NP_001306599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPSB2	ENST00000524270.6	c.733G>T	p.Gly245Cys	missense_variant	Exon 3 of 3	1	NM_032641.4	ENSP00000428338.1
SPSB2	ENST00000523102.5	c.733G>T	p.Gly245Cys	missense_variant	Exon 3 of 3	1		ENSP00000430872.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461156 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726826

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.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-0.065
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.43	.;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.40	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.13
Sift	Benign	0.070	T;T
Sift4G	Benign	0.15	T;T
Polyphen		1.0	D;D
Vest4		0.29
MutPred		0.28		Loss of disorder (P = 0.0697);Loss of disorder (P = 0.0697);
MVP		0.34
MPC		0.63
ClinPred		0.79	D
GERP RS		4.2
Varity_R		0.084
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs200625865; hg19: chr12-6980415;