rs373548222

Variant names:

• chr1-9356564-C-A
• NM_025106.4:c.673C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-9356564-C-A
• chr1-9356564-C-T

Variant summary

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

The NM_025106.4(SPSB1):​c.673C>A​(p.Arg225Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,446,496 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R225C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SPSB1 NM_025106.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.87

Genes affected

SPSB1 (HGNC:30628): (splA/ryanodine receptor domain and SOCS box containing 1) Enables ubiquitin ligase-substrate adaptor activity. Involved in protein ubiquitination and ubiquitin-dependent protein catabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPSB1	NM_025106.4	c.673C>A	p.Arg225Ser	missense_variant	Exon 2 of 3	ENST00000328089.11	NP_079382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPSB1	ENST00000328089.11	c.673C>A	p.Arg225Ser	missense_variant	Exon 2 of 3	1	NM_025106.4	ENSP00000330221.6
SPSB1	ENST00000377399.2	c.673C>A	p.Arg225Ser	missense_variant	Exon 1 of 2	1		ENSP00000366616.2
SPSB1	ENST00000357898.3	c.673C>A	p.Arg225Ser	missense_variant	Exon 2 of 3	5		ENSP00000350573.3
SPSB1	ENST00000450402.1	c.*67C>A		downstream_gene_variant		5		ENSP00000409235.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446496 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 716522

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000226

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	.;.;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.7	M;M;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Benign	0.26
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.95	P;P;P
Vest4		0.60
MutPred		0.63		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.45
MPC		1.2
ClinPred		0.97	D
GERP RS		4.2
Varity_R		0.75
gMVP		0.89

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: chr1-9416623;