Variant chr2-230370926-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138402.6(SP140L):c.542C>T(p.Pro181Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000259 in 1,613,370 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

SP140L
NM_138402.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.03

Variant links:

Genes affected

SP140L (HGNC:25105): (SP140 nuclear body protein like) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nuclear body. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SP140L links:

SP140L (HGNC:):

SP140L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007773608).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP140L	NM_138402.6 linkuse as main transcript	c.542C>T	p.Pro181Leu	missense_variant	6/19	ENST00000415673.7	NP_612411.4	Q9H930-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP140L	ENST00000415673.7 linkuse as main transcript	c.542C>T	p.Pro181Leu	missense_variant	6/19	5	NM_138402.6	ENSP00000397911.2		Q9H930-4

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000399

AC:

AN:

248298

Hom.:

AF XY:

0.000356

AC XY:

AN XY:

134712

show subpopulations

Gnomad AFR exome

AF:

0.000390

Gnomad AMR exome

AF:

0.000175

Gnomad ASJ exome

AF:

0.00627

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000160

Gnomad OTH exome

AF:

0.000830

GnomAD4 exome

AF:

0.000242

AC:

353

AN:

1461260

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

188

AN XY:

726894

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00616

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000998

Gnomad4 OTH exome

AF:

0.000663

GnomAD4 genome

AF:

0.000427

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.000387

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000478

Hom.:

Bravo

AF:

0.000457

ESP6500AA

AF:

0.000253

AC:

ESP6500EA

AF:

0.000481

AC:

ExAC

AF:

0.000314

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

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

Nov 03, 2022

The c.542C>T (p.P181L) alteration is located in exon 6 (coding exon 6) of the SP140L gene. This alteration results from a C to T substitution at nucleotide position 542, causing the proline (P) at amino acid position 181 to be replaced by a leucine (L). 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

0.079

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.19

DANN

Benign

0.93

DEOGEN2

Benign

0.019

.;T;T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.72

T;T;T;T;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.0078

T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.2

L;L;.;.;.

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-3.0

D;D;.;.;N

REVEL

Benign

0.077

Sift

Benign

0.71

T;T;.;.;D

Sift4G

Benign

0.15

T;T;T;T;T

Polyphen

0.017

.;.;.;.;B

Vest4

0.11

MVP

0.23

MPC

0.067

ClinPred

0.0048

GERP RS

-2.5

Varity_R

0.023

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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