Variant 11-129910541-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_199437.2(PRDM10):c.3098A>C(p.Gln1033Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00311 in 1,613,372 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 25 hom. )

Consequence

PRDM10
NM_199437.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.83

Variant links:

Genes affected

PRDM10 (HGNC:13995): (PR/SET domain 10) The protein encoded by this gene is a transcription factor that contains C2H2-type zinc-fingers. It also contains a positive regulatory domain, which has been found in several other zinc-finger transcription factors including those involved in B cell differentiation and tumor suppression. Studies of the mouse counterpart suggest that this protein may be involved in the development of the central nerve system (CNS), as well as in the pathogenesis of neuronal storage disease. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

PRDM10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, PRDM10

BP4

Computational evidence support a benign effect (MetaRNN=0.00473091).

BP6

Variant 11-129910541-T-G is Benign according to our data. Variant chr11-129910541-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2642544.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 330 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM10	NM_199437.2 linkuse as main transcript	c.3098A>C	p.Gln1033Pro	missense_variant	19/21	ENST00000360871.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM10	ENST00000360871.8 linkuse as main transcript	c.3098A>C	p.Gln1033Pro	missense_variant	19/21	1	NM_199437.2	P4	Q9NQV6-4

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

328

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00309

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00298

AC:

745

AN:

250096

Hom.:

AF XY:

0.00292

AC XY:

395

AN XY:

135414

show subpopulations

Gnomad AFR exome

AF:

0.000877

Gnomad AMR exome

AF:

0.00200

Gnomad ASJ exome

AF:

0.0151

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00219

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.00360

Gnomad OTH exome

AF:

0.00508

GnomAD4 exome

AF:

0.00321

AC:

4692

AN:

1461106

Hom.:

Cov.:

AF XY:

0.00323

AC XY:

2345

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.000897

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.0167

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00227

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.00327

Gnomad4 OTH exome

AF:

0.00383

GnomAD4 genome

AF:

0.00217

AC:

330

AN:

152266

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

156

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00309

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00321

Hom.:

Bravo

AF:

0.00241

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00454

AC:

ExAC

AF:

0.00291

AC:

353

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

PRDM10: PP2, BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.62

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.69

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

M_CAP

Benign

0.0060

MetaRNN

Benign

0.0047

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

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.73

D;D;N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.78

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

REVEL

Benign

0.019

Sift

Benign

0.038

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

Sift4G

Benign

0.074

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

Polyphen

0.0, 0.0010

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

Vest4

0.31

MVP

0.068

MPC

0.12

ClinPred

0.037

GERP RS

1.2

gMVP

0.43

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