Variant 4-80184069-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000508965.5(PRDM8):n.177+14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,758 control chromosomes in the GnomAD database, including 2,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 2008 hom., cov: 32)

Exomes 𝑓: 0.094 ( 8 hom. )

Consequence

PRDM8
ENST00000508965.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00300

Variant links:

Genes affected

PRDM8-AS1 (HGNC:55581): (PRDM8 antisense RNA 1)

PRDM8-AS1 links:

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-80184069-G-T is Benign according to our data. Variant chr4-80184069-G-T is described in ClinVar as [Benign]. Clinvar id is 3256813.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM8-AS1	NR_183911.1 link	n.797-645C>A		intron_variant	Intron 5 of 5
PRDM8-AS1	NR_183912.1 link	n.794-645C>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
PRDM8-AS1	ENST00000503589.1 link	n.422-645C>A	intron_variant	Intron 1 of 1	4
PRDM8	ENST00000508965.5 link	n.177+14G>T	intron_variant	Intron 1 of 3	3
PRDM8	ENST00000509375.5 link	n.175+14G>T	intron_variant	Intron 1 of 2	3
PRDM8-AS1	ENST00000653209.1 link	n.892-645C>A	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19333

AN:

152096

Hom.:

2003

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0944

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.559

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0794

Gnomad OTH

AF:

0.129

GnomAD4 exome

AF:

0.0938

AC:

AN:

544

Hom.:

Cov.:

AF XY:

0.0990

AC XY:

AN XY:

414

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.875

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.0591

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.127

AC:

19360

AN:

152214

Hom.:

2008

Cov.:

AF XY:

0.137

AC XY:

10212

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0944

Gnomad4 AMR

AF:

0.213

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.560

Gnomad4 SAS

AF:

0.268

Gnomad4 FIN

AF:

0.168

Gnomad4 NFE

AF:

0.0794

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.0432

Hom.:

Bravo

AF:

0.129

Asia WGS

AF:

0.422

AC:

1464

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 37% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 34. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.0

DANN

Benign

0.57

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