4-80191461-C-CTATAT

Position:

• chr4-80191461-C-CTATAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.60

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

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM8	NM_020226.4	c.-982-8_-982-4dupTATTA		splice_region_variant, intron_variant			NP_064611.3
PRDM8-AS1	NR_183911.1	n.486+740_486+744dupATATA		intron_variant
PRDM8-AS1	NR_183912.1	n.486+740_486+744dupATATA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM8	ENST00000339711.8	c.-982-11_-982-10insTATAT		intron_variant		1		ENSP00000339764.4
PRDM8	ENST00000515013.5	c.-982-11_-982-10insTATAT		intron_variant		1		ENSP00000425149.1
PRDM8	ENST00000504452.5	c.-772-2652_-772-2651insTATAT		intron_variant		5		ENSP00000423985.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83038 AN: 151514 Hom.: 25933 Cov.: 0

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: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.548 AC: 83152 AN: 151634 Hom.: 25983 Cov.: 0 AF XY: 0.553 AC XY: 40995 AN XY: 74108

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

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 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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10635793; hg19: chr4-81112615;