Variant chr3-141066382-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_080862.3(SPSB4):c.278A>G(p.His93Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000287 in 1,394,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

SPSB4
NM_080862.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28881192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPSB4	NM_080862.3 link	c.278A>G	p.His93Arg	missense_variant	2/3	ENST00000310546.3	NP_543138.1	Q96A44
SPSB4	XM_017007509.3 link	c.278A>G	p.His93Arg	missense_variant	2/3		XP_016862998.1
SPSB4	XR_924215.4 link	n.1077A>G		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPSB4	ENST00000310546.3 link	c.278A>G	p.His93Arg	missense_variant	2/3	1	NM_080862.3	ENSP00000311609.2		Q96A44

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

143538

Hom.:

AF XY:

0.0000129

AC XY:

AN XY:

77608

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000287

AC:

AN:

1394438

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688080

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000844

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:

9.26e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 10, 2024

The c.278A>G (p.H93R) alteration is located in exon 3 (coding exon 1) of the SPSB4 gene. This alteration results from a A to G substitution at nucleotide position 278, causing the histidine (H) at amino acid position 93 to be replaced by an arginine (R). 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

Uncertain

0.52

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

Eigen

Benign

0.00051

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.030

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.17

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Polyphen

0.57

Vest4

0.28

MutPred

0.70

Gain of methylation at H93 (P = 0.0135);

MVP

0.31

MPC

0.96

ClinPred

0.23

GERP RS

4.3

Varity_R

0.90

gMVP

0.54

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