Variant chr2-138551027-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001001664.3(SPOPL):c.325G>C(p.Ala109Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,994 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SPOPL
NM_001001664.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.00

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPOPL	NM_001001664.3 linkuse as main transcript	c.325G>C	p.Ala109Pro	missense_variant	4/11	ENST00000280098.9	NP_001001664.1	Q6IQ16
SPOPL	XM_047444115.1 linkuse as main transcript	c.3G>C	p.Met1?	start_lost	2/10		XP_047300071.1
SPOPL	XM_047444116.1 linkuse as main transcript	c.3G>C	p.Met1?	start_lost	2/10		XP_047300072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPOPL	ENST00000280098.9 linkuse as main transcript	c.325G>C	p.Ala109Pro	missense_variant	4/11	1	NM_001001664.3	ENSP00000280098.4	Q6IQ16
SPOPL	ENST00000420679.1 linkuse as main transcript	n.325G>C		non_coding_transcript_exon_variant	3/11	5		ENSP00000396006.1	F8WD02
SPOPL	ENST00000430968.5 linkuse as main transcript	n.*35G>C		non_coding_transcript_exon_variant	4/5	5		ENSP00000410201.1	F8WBB7
SPOPL	ENST00000430968.5 linkuse as main transcript	n.*35G>C		3_prime_UTR_variant	4/5	5		ENSP00000410201.1	F8WBB7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250392

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135410

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460994

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726788

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

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

Jul 13, 2021

The c.325G>C (p.A109P) alteration is located in exon 4 (coding exon 3) of the SPOPL gene. This alteration results from a G to C substitution at nucleotide position 325, causing the alanine (A) at amino acid position 109 to be replaced by a proline (P). 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

0.69

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.96

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.22

Sift

Uncertain

0.0060

Sift4G

Benign

0.092

Polyphen

0.95

Vest4

0.60

MutPred

0.55

Gain of glycosylation at A109 (P = 0.0209);

MVP

0.89

MPC

0.83

ClinPred

0.87

GERP RS

5.5

Varity_R

0.64

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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