rs12780

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001099403.2(PRDM8):c.1980G>C(p.Arg660Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,612,362 control chromosomes in the GnomAD database, including 67,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6195 hom., cov: 31)

Exomes 𝑓: 0.28 ( 61742 hom. )

Consequence

PRDM8
NM_001099403.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.583

Variant links:

Genes affected

PRDM8 (HGNC:13993): (PR/SET domain 8) This gene encodes a protein that belongs to a conserved family of histone methyltransferases that predominantly act as negative regulators of transcription. The encoded protein contains an N-terminal Su(var)3-9, Enhancer-of-zeste, and Trithorax (SET) domain and a double zinc-finger domain. Knockout of this gene in mouse results in mistargeting by neurons of the dorsal telencephalon, abnormal itch-like behavior, and impaired differentiation of rod bipolar cells. In humans, the protein has been shown to interact with the phosphatase laforin and the ubiquitin ligase malin, which regulate glycogen construction in the cytoplasm. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

PRDM8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 4-80203442-G-C is Benign according to our data. Variant chr4-80203442-G-C is described in ClinVar as [Benign]. Clinvar id is 1170071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.583 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM8	NM_001099403.2 link	c.1980G>C	p.Arg660Arg	synonymous_variant	Exon 4 of 4	ENST00000415738.3	NP_001092873.1	Q9NQV8-1A0A024RDC4Q05CA1
PRDM8	NM_020226.4 link	c.1980G>C	p.Arg660Arg	synonymous_variant	Exon 10 of 10		NP_064611.3	Q9NQV8-1A0A024RDC4Q05CA1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRDM8	ENST00000415738.3 link	c.1980G>C	p.Arg660Arg	synonymous_variant	Exon 4 of 4	1	NM_001099403.2	ENSP00000406998.2	Q9NQV8-1
PRDM8	ENST00000339711.8 link	c.1980G>C	p.Arg660Arg	synonymous_variant	Exon 10 of 10	1		ENSP00000339764.4	Q9NQV8-1
PRDM8	ENST00000504452.5 link	c.1980G>C	p.Arg660Arg	synonymous_variant	Exon 8 of 8	5		ENSP00000423985.1	Q9NQV8-1

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41388

AN:

151836

Hom.:

6188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.617

Gnomad SAS

AF:

0.384

Gnomad FIN

AF:

0.357

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.284

GnomAD3 exomes

AF:

0.321

AC:

78956

AN:

245986

Hom.:

14007

AF XY:

0.320

AC XY:

42797

AN XY:

133578

show subpopulations

Gnomad AFR exome

AF:

0.185

Gnomad AMR exome

AF:

0.366

Gnomad ASJ exome

AF:

0.262

Gnomad EAS exome

AF:

0.632

Gnomad SAS exome

AF:

0.370

Gnomad FIN exome

AF:

0.352

Gnomad NFE exome

AF:

0.263

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.281

AC:

410148

AN:

1460412

Hom.:

61742

Cov.:

AF XY:

0.283

AC XY:

205600

AN XY:

726324

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.365

Gnomad4 ASJ exome

AF:

0.269

Gnomad4 EAS exome

AF:

0.618

Gnomad4 SAS exome

AF:

0.368

Gnomad4 FIN exome

AF:

0.349

Gnomad4 NFE exome

AF:

0.258

Gnomad4 OTH exome

AF:

0.291

GnomAD4 genome

AF:

0.273

AC:

41416

AN:

151950

Hom.:

6195

Cov.:

AF XY:

0.284

AC XY:

21079

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.332

Gnomad4 ASJ

AF:

0.276

Gnomad4 EAS

AF:

0.618

Gnomad4 SAS

AF:

0.383

Gnomad4 FIN

AF:

0.357

Gnomad4 NFE

AF:

0.262

Gnomad4 OTH

AF:

0.283

Alfa

AF:

0.259

Hom.:

1682

Bravo

AF:

0.266

Asia WGS

AF:

0.487

AC:

1688

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Early-onset Lafora body disease

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jun 25, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 70% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 65. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.5

DANN

Benign

0.79

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