Variant rs755316101 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP3BP6_Moderate

The NM_001099403.2(PRDM8):c.1778_1795del(p.Ala593_Ala598del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000404 in 1,556,336 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 1 hom. )

Consequence

PRDM8
NM_001099403.2 inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.29

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 Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_001099403.2

BP6

Variant 4-80203232-AGCCGCGGCTGCGGCGGCG-A is Benign according to our data. Variant chr4-80203232-AGCCGCGGCTGCGGCGGCG-A is described in ClinVar as [Benign]. Clinvar id is 475674.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM8	NM_001099403.2 linkuse as main transcript	c.1778_1795del	p.Ala593_Ala598del	inframe_deletion	4/4	ENST00000415738.3	NP_001092873.1
PRDM8	NM_020226.4 linkuse as main transcript	c.1778_1795del	p.Ala593_Ala598del	inframe_deletion	10/10		NP_064611.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM8	ENST00000415738.3 linkuse as main transcript	c.1778_1795del	p.Ala593_Ala598del	inframe_deletion	4/4	1	NM_001099403.2	ENSP00000406998	P1	Q9NQV8-1
PRDM8	ENST00000339711.8 linkuse as main transcript	c.1778_1795del	p.Ala593_Ala598del	inframe_deletion	10/10	1		ENSP00000339764	P1	Q9NQV8-1
PRDM8	ENST00000504452.5 linkuse as main transcript	c.1778_1795del	p.Ala593_Ala598del	inframe_deletion	8/8	5		ENSP00000423985	P1	Q9NQV8-1

Frequencies

GnomAD3 genomes

AF:

0.000751

AC:

114

AN:

151748

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00823

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000339

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000936

AC:

145

AN:

154892

Hom.:

AF XY:

0.00106

AC XY:

AN XY:

85042

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000161

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000415

Gnomad FIN exome

AF:

0.00783

Gnomad NFE exome

AF:

0.000285

Gnomad OTH exome

AF:

0.000699

GnomAD4 exome

AF:

0.000367

AC:

515

AN:

1404478

Hom.:

AF XY:

0.000360

AC XY:

250

AN XY:

694036

show subpopulations

Gnomad4 AFR exome

AF:

0.0000631

Gnomad4 AMR exome

AF:

0.000167

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000546

Gnomad4 SAS exome

AF:

0.0000371

Gnomad4 FIN exome

AF:

0.00591

Gnomad4 NFE exome

AF:

0.000181

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000751

AC:

114

AN:

151858

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00823

Gnomad4 NFE

AF:

0.000339

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000473

Hom.:

Bravo

AF:

0.000140

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early-onset Lafora body disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 09, 2023

- -

PRDM8-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 26, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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