Genetic Variant PRDM8:c.-744+14G>T (chr4-80184069-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000861821.1(PRDM8):c.-744+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
ENST00000861821.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00300

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 links:

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

PRDM8-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000861821.1. 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-AS1	NR_183911.1		n.797-645C>A		intron	N/A
	PRDM8-AS1	NR_183912.1		n.794-645C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
PRDM8	ENST00000861821.1	c.-744+14G>T	intron	N/A	ENSP00000531880.1
PRDM8	ENST00000952373.1	c.-983+14G>T	intron	N/A	ENSP00000622432.1
PRDM8	ENST00000952374.1	c.-392+14G>T	intron	N/A	ENSP00000622433.1

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

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.125

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.875

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0591

AC:

AN:

474

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.127

AC:

19360

AN:

152214

Hom.:

2008

Cov.:

AF XY:

0.137

AC XY:

10212

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0944

AC:

3923

AN:

41560

American (AMR)

AF:

0.213

AC:

3255

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

355

AN:

3470

East Asian (EAS)

AF:

0.560

AC:

2874

AN:

5132

South Asian (SAS)

AF:

0.268

AC:

1296

AN:

4832

European-Finnish (FIN)

AF:

0.168

AC:

1788

AN:

10612

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0794

AC:

5402

AN:

67994

Other (OTH)

AF:

0.133

AC:

281

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

800

1599

2399

3198

3998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.0432

Hom.:

Bravo

AF:

0.129

Asia WGS

AF:

0.422

AC:

1464

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.0

(source)

DANN

Benign

0.57

PhyloP100

0.0030

PromoterAI

-0.0070

Neutral

(source)

Splicing

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

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