Variant chr2-138550550-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001001664.3(SPOPL):c.146G>A(p.Gly49Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SPOPL
NM_001001664.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

Variant links:

Genes affected

SPOPL (HGNC:27934): (speckle type BTB/POZ protein like) Predicted to enable ubiquitin protein ligase binding activity. Involved in negative regulation of protein ubiquitination and proteasome-mediated ubiquitin-dependent protein catabolic process. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

SPOPL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.823

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPOPL	NM_001001664.3 linkuse as main transcript	c.146G>A	p.Gly49Asp	missense_variant	3/11	ENST00000280098.9	NP_001001664.1	Q6IQ16
SPOPL	XM_047444115.1 linkuse as main transcript	c.-106G>A		5_prime_UTR_premature_start_codon_gain_variant	1/10		XP_047300071.1
SPOPL	XM_047444115.1 linkuse as main transcript	c.-106G>A		5_prime_UTR_variant	1/10		XP_047300071.1
SPOPL	XM_047444116.1 linkuse as main transcript	c.-52+256G>A		intron_variant			XP_047300072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPOPL	ENST00000280098.9 linkuse as main transcript	c.146G>A	p.Gly49Asp	missense_variant	3/11	1	NM_001001664.3	ENSP00000280098.4	Q6IQ16
SPOPL	ENST00000420679.1 linkuse as main transcript	n.146G>A		non_coding_transcript_exon_variant	2/11	5		ENSP00000396006.1	F8WD02
SPOPL	ENST00000430968.5 linkuse as main transcript	n.146G>A		non_coding_transcript_exon_variant	3/5	5		ENSP00000410201.1	F8WBB7

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250566

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135468

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

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

Sep 27, 2024

The c.146G>A (p.G49D) alteration is located in exon 3 (coding exon 2) of the SPOPL gene. This alteration results from a G to A substitution at nucleotide position 146, causing the glycine (G) at amino acid position 49 to be replaced by an aspartic acid (D). 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

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.046

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.4

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-4.4

REVEL

Uncertain

0.57

Sift

Benign

0.20

Sift4G

Uncertain

0.023

Polyphen

1.0

Vest4

0.85

MVP

0.90

MPC

0.89

ClinPred

0.98

GERP RS

4.9

Varity_R

0.59

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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