Variant 3-141066621-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000310546.3(SPSB4):c.517C>G(p.Leu173Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000551 in 1,452,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SPSB4
ENST00000310546.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.259

Variant links:

Genes affected

SPSB4 (HGNC:30630): (splA/ryanodine receptor domain and SOCS box containing 4) Enables ubiquitin ligase-substrate adaptor activity. Involved in cellular protein metabolic process; positive regulation of protein polyubiquitination; and regulation of circadian rhythm. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

SPSB4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.035376668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SPSB4	NM_080862.3 linkuse as main transcript	c.517C>G	p.Leu173Val	missense_variant	2/3	ENST00000310546.3	NP_543138.1
SPSB4	XM_017007509.3 linkuse as main transcript	c.517C>G	p.Leu173Val	missense_variant	2/3		XP_016862998.1
SPSB4	XR_924215.4 linkuse as main transcript	n.1316C>G		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPSB4	ENST00000310546.3 linkuse as main transcript	c.517C>G	p.Leu173Val	missense_variant	2/3	1	NM_080862.3	ENSP00000311609	P1
SPSB4	ENST00000508126.1 linkuse as main transcript			upstream_gene_variant		2		ENSP00000422034

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000551

AC:

AN:

1452908

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

721962

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000632

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000227

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.517C>G (p.L173V) alteration is located in exon 3 (coding exon 1) of the SPSB4 gene. This alteration results from a C to G substitution at nucleotide position 517, causing the leucine (L) at amino acid position 173 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.24

DEOGEN2

Benign

0.051

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.36

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.016

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.5

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.64

PROVEAN

Benign

2.0

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.059

MutPred

0.44

Loss of glycosylation at S176 (P = 0.1175);

MVP

0.26

MPC

0.53

ClinPred

0.083

GERP RS

3.2

Varity_R

0.31

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over