Variant rs28405693 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001099403.2(PRDM8):c.1726C>T(p.Leu576Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00934 in 1,550,366 control chromosomes in the GnomAD database, including 697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 347 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 350 hom. )

Consequence

PRDM8
NM_001099403.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.11

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 4-80203188-C-T is Benign according to our data. Variant chr4-80203188-C-T is described in ClinVar as [Benign]. Clinvar id is 475673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM8	NM_001099403.2 linkuse as main transcript	c.1726C>T	p.Leu576Leu	synonymous_variant	4/4	ENST00000415738.3	NP_001092873.1	Q9NQV8-1A0A024RDC4Q05CA1
PRDM8	NM_020226.4 linkuse as main transcript	c.1726C>T	p.Leu576Leu	synonymous_variant	10/10		NP_064611.3	Q9NQV8-1A0A024RDC4Q05CA1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRDM8	ENST00000415738.3 linkuse as main transcript	c.1726C>T	p.Leu576Leu	synonymous_variant	4/4	1	NM_001099403.2	ENSP00000406998.2	Q9NQV8-1
PRDM8	ENST00000339711.8 linkuse as main transcript	c.1726C>T	p.Leu576Leu	synonymous_variant	10/10	1		ENSP00000339764.4	Q9NQV8-1
PRDM8	ENST00000504452.5 linkuse as main transcript	c.1726C>T	p.Leu576Leu	synonymous_variant	8/8	5		ENSP00000423985.1	Q9NQV8-1

Frequencies

GnomAD3 genomes

AF:

0.0389

AC:

5911

AN:

151876

Hom.:

344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0188

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0472

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.0306

GnomAD3 exomes

AF:

0.0145

AC:

2075

AN:

143544

Hom.:

AF XY:

0.0130

AC XY:

1022

AN XY:

78896

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.0163

Gnomad ASJ exome

AF:

0.000123

Gnomad EAS exome

AF:

0.0428

Gnomad SAS exome

AF:

0.0109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000569

Gnomad OTH exome

AF:

0.0125

GnomAD4 exome

AF:

0.00610

AC:

8534

AN:

1398384

Hom.:

350

Cov.:

AF XY:

0.00580

AC XY:

4009

AN XY:

690996

show subpopulations

Gnomad4 AFR exome

AF:

0.128

Gnomad4 AMR exome

AF:

0.0186

Gnomad4 ASJ exome

AF:

0.000239

Gnomad4 EAS exome

AF:

0.0486

Gnomad4 SAS exome

AF:

0.0106

Gnomad4 FIN exome

AF:

0.0000479

Gnomad4 NFE exome

AF:

0.000367

Gnomad4 OTH exome

AF:

0.0125

GnomAD4 genome

AF:

0.0391

AC:

5939

AN:

151982

Hom.:

347

Cov.:

AF XY:

0.0380

AC XY:

2822

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.0187

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0472

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.000662

Gnomad4 OTH

AF:

0.0303

Alfa

AF:

0.0176

Hom.:

Bravo

AF:

0.0445

Asia WGS

AF:

0.0360

AC:

125

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Early-onset Lafora body disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.97

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