Variant 4-80202449-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000415738.3(PRDM8):c.987G>T(p.Leu329=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,546,432 control chromosomes in the GnomAD database, including 1,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L329L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.062 ( 952 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 813 hom. )

Consequence

PRDM8
ENST00000415738.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.10

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 4-80202449-G-T is Benign according to our data. Variant chr4-80202449-G-T is described in ClinVar as [Benign]. Clinvar id is 475686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM8	NM_001099403.2 linkuse as main transcript	c.987G>T	p.Leu329=	synonymous_variant	4/4	ENST00000415738.3	NP_001092873.1
PRDM8	NM_020226.4 linkuse as main transcript	c.987G>T	p.Leu329=	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.987G>T	p.Leu329=	synonymous_variant	4/4	1	NM_001099403.2	ENSP00000406998	P1	Q9NQV8-1
PRDM8	ENST00000339711.8 linkuse as main transcript	c.987G>T	p.Leu329=	synonymous_variant	10/10	1		ENSP00000339764	P1	Q9NQV8-1
PRDM8	ENST00000515013.5 linkuse as main transcript	c.987G>T	p.Leu329=	synonymous_variant	10/10	1		ENSP00000425149
PRDM8	ENST00000504452.5 linkuse as main transcript	c.987G>T	p.Leu329=	synonymous_variant	8/8	5		ENSP00000423985	P1	Q9NQV8-1

Frequencies

GnomAD3 genomes

AF:

0.0616

AC:

9363

AN:

151908

Hom.:

944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000779

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.000986

Gnomad OTH

AF:

0.0489

GnomAD3 exomes

AF:

0.0133

AC:

1878

AN:

141084

Hom.:

165

AF XY:

0.0108

AC XY:

828

AN XY:

76656

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.0139

Gnomad ASJ exome

AF:

0.000974

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000579

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00133

Gnomad OTH exome

AF:

0.00871

GnomAD4 exome

AF:

0.00675

AC:

9413

AN:

1394406

Hom.:

813

Cov.:

AF XY:

0.00603

AC XY:

4147

AN XY:

688014

show subpopulations

Gnomad4 AFR exome

AF:

0.223

Gnomad4 AMR exome

AF:

0.0149

Gnomad4 ASJ exome

AF:

0.00116

Gnomad4 EAS exome

AF:

0.0000839

Gnomad4 SAS exome

AF:

0.000669

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000669

Gnomad4 OTH exome

AF:

0.0169

GnomAD4 genome

AF:

0.0618

AC:

9396

AN:

152026

Hom.:

952

Cov.:

AF XY:

0.0596

AC XY:

4434

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.210

Gnomad4 AMR

AF:

0.0313

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000781

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000986

Gnomad4 OTH

AF:

0.0502

Alfa

AF:

0.00395

Hom.:

Bravo

AF:

0.0707

Asia WGS

AF:

0.0300

AC:

104

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.6

DANN

Benign

0.74

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