Variant 17-49611390-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP2

The NM_001007228.2(SPOP):c.548A>C(p.Glu183Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SPOP
NM_001007228.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

Variant links:

Genes affected

SPOP (HGNC:11254): (speckle type BTB/POZ protein) This gene encodes a protein that may modulate the transcriptional repression activities of death-associated protein 6 (DAXX), which interacts with histone deacetylase, core histones, and other histone-associated proteins. In mouse, the encoded protein binds to the putative leucine zipper domain of macroH2A1.2, a variant H2A histone that is enriched on inactivated X chromosomes. The BTB/POZ domain of this protein has been shown in other proteins to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes. Alternative splicing of this gene results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

SPOP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1

In a region_of_interest Required for nuclear localization (size 120) in uniprot entity SPOP_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_001007228.2

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SPOP. . Trascript score misZ 5.5316 (greater than threshold 3.09). GenCC has associacion of gene with neurodevelopmental disorder with microcephaly and dysmorphic facies.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPOP	NM_001007228.2 linkuse as main transcript	c.548A>C	p.Glu183Ala	missense_variant	6/10	ENST00000504102.6	NP_001007229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPOP	ENST00000504102.6 linkuse as main transcript	c.548A>C	p.Glu183Ala	missense_variant	6/10	1	NM_001007228.2	ENSP00000425905	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Jun 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.57

D;D;D;D;.;T;.

Eigen

Benign

0.086

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.98

.;D;.;.;D;D;D

M_CAP

Benign

0.076

MetaRNN

Uncertain

0.53

D;D;D;D;D;D;D

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.4

L;L;L;L;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.7

D;D;D;D;D;D;D

REVEL

Uncertain

0.39

Sift

Uncertain

0.027

D;D;D;D;D;D;D

Sift4G

Benign

0.29

T;T;T;T;.;T;.

Polyphen

0.20

B;B;B;B;.;.;.

Vest4

0.39

MutPred

0.42

Gain of ubiquitination at K180 (P = 0.115);Gain of ubiquitination at K180 (P = 0.115);Gain of ubiquitination at K180 (P = 0.115);Gain of ubiquitination at K180 (P = 0.115);Gain of ubiquitination at K180 (P = 0.115);Gain of ubiquitination at K180 (P = 0.115);Gain of ubiquitination at K180 (P = 0.115);

MVP

0.69

ClinPred

0.95

GERP RS

5.5

Varity_R

0.47

gMVP

0.67

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over