Variant 4-80191461-C-CTATAT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_020226.4(PRDM8):c.-982-8_-982-4dupTATTA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.55 ( 25983 hom., cov: 0)

Failed GnomAD Quality Control

Consequence

PRDM8
NM_020226.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.60

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:

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

PRDM8-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 4-80191461-C-CTATAT is Benign according to our data. Variant chr4-80191461-C-CTATAT is described in ClinVar as [Benign]. Clinvar id is 3256798.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
PRDM8	NM_020226.4 link	c.-982-8_-982-4dupTATTA	splice_region_variant, intron_variant	Intron 1 of 9	NP_064611.3	Q9NQV8-1A0A024RDC4Q05CA1
PRDM8-AS1	NR_183911.1 link	n.486+740_486+744dupATATA	intron_variant	Intron 3 of 5
PRDM8-AS1	NR_183912.1 link	n.486+740_486+744dupATATA	intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
PRDM8	ENST00000339711.8 link	c.-982-11_-982-10insTATAT	intron_variant	Intron 1 of 9	1	ENSP00000339764.4	Q9NQV8-1
PRDM8	ENST00000515013.5 link	c.-982-11_-982-10insTATAT	intron_variant	Intron 1 of 9	1	ENSP00000425149.1	E9PEH0
PRDM8	ENST00000504452.5 link	c.-772-2652_-772-2651insTATAT	intron_variant	Intron 1 of 7	5	ENSP00000423985.1	Q9NQV8-1

Frequencies

GnomAD3 genomes

AF:

0.548

AC:

83038

AN:

151514

Hom.:

25933

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

0.338

Gnomad AMR

AF:

0.524

Gnomad ASJ

AF:

0.432

Gnomad EAS

AF:

0.806

Gnomad SAS

AF:

0.628

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.526

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.546

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

GnomAD4 genome

AF:

0.548

AC:

83152

AN:

151634

Hom.:

25983

Cov.:

AF XY:

0.553

AC XY:

40995

AN XY:

74108

show subpopulations

Gnomad4 AFR

AF:

0.847

Gnomad4 AMR

AF:

0.524

Gnomad4 ASJ

AF:

0.432

Gnomad4 EAS

AF:

0.806

Gnomad4 SAS

AF:

0.628

Gnomad4 FIN

AF:

0.402

Gnomad4 NFE

AF:

0.378

Gnomad4 OTH

AF:

0.547

Alfa

AF:

0.470

Hom.:

2076

Asia WGS

AF:

0.744

AC:

2581

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 31, 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 67% 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: 62. Only high quality variants are reported. -

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