Variant rs144810863 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001099403.2(PRDM8):c.1137C>A(p.Gly379=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000875 in 1,532,508 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 4 hom. )

Consequence

PRDM8
NM_001099403.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00300

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 4-80202599-C-A is Benign according to our data. Variant chr4-80202599-C-A is described in ClinVar as [Benign]. Clinvar id is 475664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.003 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM8	NM_001099403.2 linkuse as main transcript	c.1137C>A	p.Gly379=	synonymous_variant	4/4	ENST00000415738.3	NP_001092873.1
PRDM8	NM_020226.4 linkuse as main transcript	c.1137C>A	p.Gly379=	synonymous_variant	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.1137C>A	p.Gly379=	synonymous_variant	4/4	1	NM_001099403.2	ENSP00000406998	P1	Q9NQV8-1
PRDM8	ENST00000339711.8 linkuse as main transcript	c.1137C>A	p.Gly379=	synonymous_variant	10/10	1		ENSP00000339764	P1	Q9NQV8-1
PRDM8	ENST00000515013.5 linkuse as main transcript	c.1137C>A	p.Gly379=	synonymous_variant	10/10	1		ENSP00000425149
PRDM8	ENST00000504452.5 linkuse as main transcript	c.1137C>A	p.Gly379=	synonymous_variant	8/8	5		ENSP00000423985	P1	Q9NQV8-1

Frequencies

GnomAD3 genomes

AF:

0.00429

AC:

653

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000944

AC:

120

AN:

127094

Hom.:

AF XY:

0.000788

AC XY:

AN XY:

69774

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000453

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000104

Gnomad OTH exome

AF:

0.000253

GnomAD4 exome

AF:

0.000496

AC:

684

AN:

1380270

Hom.:

Cov.:

AF XY:

0.000435

AC XY:

296

AN XY:

681086

show subpopulations

Gnomad4 AFR exome

AF:

0.0161

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.0000400

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000928

Gnomad4 OTH exome

AF:

0.000745

GnomAD4 genome

AF:

0.00432

AC:

657

AN:

152238

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

320

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00265

Hom.:

Bravo

AF:

0.00482

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

Jan 28, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

PRDM8-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 12, 2019

This variant is classified as 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

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.94

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