Variant 2-230461316-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001080391.2(SP100):c.875G>A(p.Arg292Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00546 in 1,614,036 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 37 hom. )

Consequence

SP100
NM_001080391.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -8.43

Variant links:

Genes affected

SP100 (HGNC:11206): (SP100 nuclear antigen) This gene encodes a subnuclear organelle and major component of the PML (promyelocytic leukemia)-SP100 nuclear bodies. PML and SP100 are covalently modified by the SUMO-1 modifier, which is considered crucial to nuclear body interactions. The encoded protein binds heterochromatin proteins and is thought to play a role in tumorigenesis, immunity, and gene regulation. Alternatively spliced variants have been identified for this gene; one of which encodes a high-mobility group protein. [provided by RefSeq, Aug 2011]

SP100 links:

LOC101928816 (HGNC:):

LOC101928816 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038842857).

BP6

Variant 2-230461316-G-A is Benign according to our data. Variant chr2-230461316-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 780026.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP100	NM_001080391.2 linkuse as main transcript	c.875G>A	p.Arg292Gln	missense_variant	9/29	ENST00000340126.9
LOC101928816	XR_427235.4 linkuse as main transcript	n.472-17951C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP100	ENST00000340126.9 linkuse as main transcript	c.875G>A	p.Arg292Gln	missense_variant	9/29	1	NM_001080391.2	P1	P23497-4

Frequencies

GnomAD3 genomes

AF:

0.00384

AC:

585

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00321

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00611

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00387

AC:

971

AN:

251074

Hom.:

AF XY:

0.00433

AC XY:

587

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00249

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00389

Gnomad FIN exome

AF:

0.00393

Gnomad NFE exome

AF:

0.00562

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00563

AC:

8233

AN:

1461726

Hom.:

Cov.:

AF XY:

0.00570

AC XY:

4146

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.00241

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00390

Gnomad4 FIN exome

AF:

0.00393

Gnomad4 NFE exome

AF:

0.00643

Gnomad4 OTH exome

AF:

0.00568

GnomAD4 genome

AF:

0.00383

AC:

583

AN:

152310

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

276

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00321

Gnomad4 NFE

AF:

0.00610

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00550

Hom.:

Bravo

AF:

0.00393

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00558

AC:

ExAC

AF:

0.00395

AC:

480

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00660

EpiControl

AF:

0.00759

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

Cadd

Benign

0.0040

Dann

Benign

0.65

DEOGEN2

Benign

0.0079

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

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0065

LIST_S2

Uncertain

0.87

D;T;T;T;D;D;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.0039

T;T;T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.34

N;.;.;N;N;N;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

0.11

N;N;N;N;N;N;N

REVEL

Benign

0.013

Sift

Benign

0.56

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

Sift4G

Benign

0.30

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

Polyphen

0.47

P;.;B;B;.;B;.

Vest4

0.23

MVP

0.52

MPC

0.34

ClinPred

0.0077

GERP RS

-8.3

Varity_R

0.0084

gMVP

0.073

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