rs201251555

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001099403.2(PRDM8):c.1390C>T(p.Pro464Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000743 in 1,233,840 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P464P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0037 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 5 hom. )

Consequence

PRDM8
NM_001099403.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0550

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

early-onset Lafora body disease
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

PRDM8 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001099403.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00395).

BP6

Variant 4-80202852-C-T is Benign according to our data. Variant chr4-80202852-C-T is described in ClinVar as Benign. ClinVar VariationId is 475668.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099403.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM8	NM_001099403.2	MANE Select	c.1390C>T	p.Pro464Ser	missense	Exon 4 of 4	NP_001092873.1	Q9NQV8-1
	PRDM8	NM_020226.4		c.1390C>T	p.Pro464Ser	missense	Exon 10 of 10	NP_064611.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRDM8	ENST00000415738.3	TSL:1 MANE Select	c.1390C>T	p.Pro464Ser	missense	Exon 4 of 4	ENSP00000406998.2	Q9NQV8-1
PRDM8	ENST00000339711.8	TSL:1	c.1390C>T	p.Pro464Ser	missense	Exon 10 of 10	ENSP00000339764.4	Q9NQV8-1
PRDM8	ENST00000952376.1		c.1393C>T	p.Pro465Ser	missense	Exon 4 of 4	ENSP00000622435.1

Frequencies

GnomAD3 genomes

AF:

0.00370

AC:

559

AN:

150932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000792

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:

0.0000739

Gnomad OTH

AF:

0.00338

GnomAD2 exomes

AF:

0.00

AC:

AN:

106

AF XY:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000331

AC:

358

AN:

1082800

Hom.:

Cov.:

AF XY:

0.000317

AC XY:

163

AN XY:

514854

show subpopulations

African (AFR)

AF:

0.0145

AC:

320

AN:

22098

American (AMR)

AF:

0.000390

AC:

AN:

7684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13386

East Asian (EAS)

AF:

0.00

AC:

AN:

24494

South Asian (SAS)

AF:

0.0000459

AC:

AN:

21770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21636

Middle Eastern (MID)

AF:

0.000349

AC:

AN:

2868

European-Non Finnish (NFE)

AF:

0.00000216

AC:

AN:

925784

Other (OTH)

AF:

0.000720

AC:

AN:

43080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00370

AC:

559

AN:

151040

Hom.:

Cov.:

AF XY:

0.00374

AC XY:

276

AN XY:

73804

show subpopulations

African (AFR)

AF:

0.0129

AC:

535

AN:

41412

American (AMR)

AF:

0.000791

AC:

AN:

15172

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10148

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000739

AC:

AN:

67616

Other (OTH)

AF:

0.00334

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00203

Hom.:

Asia WGS

AF:

0.000607

AC:

AN:

3308

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Early-onset Lafora body disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.025

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

0.055

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.3

REVEL

Benign

0.022

Sift

Benign

0.16

Sift4G

Benign

0.34

Varity_R

0.036

gMVP

0.21

Mutation Taster

=98/2

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over