Variant 1-9356175-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_025106.4(SPSB1):c.284G>A(p.Arg95His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000976 in 1,434,600 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000098 ( 0 hom. )

Consequence

SPSB1
NM_025106.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.93

Variant links:

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]

SPSB1 links:

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ACMG classification

Classification made for transcript

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/exons	MANE	UniProt
SPSB1	NM_025106.4 linkuse as main transcript	c.284G>A	p.Arg95His	missense_variant	2/3	ENST00000328089.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SPSB1	ENST00000328089.11 linkuse as main transcript	c.284G>A	p.Arg95His	missense_variant	2/3	1	NM_025106.4	P1
SPSB1	ENST00000377399.2 linkuse as main transcript	c.284G>A	p.Arg95His	missense_variant	1/2	1		P1
SPSB1	ENST00000357898.3 linkuse as main transcript	c.284G>A	p.Arg95His	missense_variant	2/3	5		P1
SPSB1	ENST00000450402.1 linkuse as main transcript	c.284G>A	p.Arg95His	missense_variant	2/2	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000862

AC:

AN:

232114

Hom.:

AF XY:

0.00000806

AC XY:

AN XY:

124054

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000397

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000976

AC:

AN:

1434600

Hom.:

Cov.:

AF XY:

0.00000845

AC XY:

AN XY:

709746

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000246

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000100

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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 03, 2021

The c.284G>A (p.R95H) alteration is located in exon 2 (coding exon 1) of the SPSB1 gene. This alteration results from a G to A substitution at nucleotide position 284, causing the arginine (R) at amino acid position 95 to be replaced by a histidine (H). 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

0.20

BayesDel_addAF

Benign

-0.0094

BayesDel_noAF

Benign

-0.14

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.30

T;.;T;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.65

D;D;D;D

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.4

M;.;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-4.1

D;D;D;D

REVEL

Benign

0.29

Sift

Benign

0.14

T;T;T;T

Sift4G

Benign

0.14

T;T;T;T

Polyphen

0.55

P;.;P;P

Vest4

0.72

MutPred

0.48

Loss of MoRF binding (P = 0.0135);Loss of MoRF binding (P = 0.0135);Loss of MoRF binding (P = 0.0135);Loss of MoRF binding (P = 0.0135);

MVP

0.42

MPC

1.4

ClinPred

0.91

GERP RS

5.2

Varity_R

0.39

gMVP

0.74

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