rs755420089

Variant names:

• chr1-9356034-A-C
• NM_025106.4:c.143A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-9356034-A-C
• chr1-9356034-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025106.4(SPSB1):​c.143A>C​(p.Tyr48Ser) 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 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y48C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SPSB1 NM_025106.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06257072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPSB1	NM_025106.4	c.143A>C	p.Tyr48Ser	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.143A>C	p.Tyr48Ser	missense_variant	Exon 2 of 3	1	NM_025106.4	ENSP00000330221.6
SPSB1	ENST00000377399.2	c.143A>C	p.Tyr48Ser	missense_variant	Exon 1 of 2	1		ENSP00000366616.2
SPSB1	ENST00000357898.3	c.143A>C	p.Tyr48Ser	missense_variant	Exon 2 of 3	5		ENSP00000350573.3
SPSB1	ENST00000450402.1	c.143A>C	p.Tyr48Ser	missense_variant	Exon 2 of 2	5		ENSP00000409235.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461826 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

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: 8.99e-7

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	Benign	0.059
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.75
DEOGEN2	Benign	0.067	T;.;T;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.80	.;T;.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.063	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;.;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.23	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.76	T;T;T;T
Sift4G	Benign	0.73	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.15
MutPred		0.38		Gain of disorder (P = 0.0051);Gain of disorder (P = 0.0051);Gain of disorder (P = 0.0051);Gain of disorder (P = 0.0051);
MVP		0.40
MPC		1.3
ClinPred		0.099	T
GERP RS		5.3
Varity_R		0.47
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-9416093;