Genetic Variant PRDM14:p.Asp543Asp (chr8-70052164-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_024504.4(PRDM14):c.1629T>C(p.Asp543Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,612,438 control chromosomes in the GnomAD database, including 317,336 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.62 ( 29629 hom., cov: 33)

Exomes 𝑓: 0.63 ( 287707 hom. )

Consequence

PRDM14
NM_024504.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.519

Variant links:

Genes affected

PRDM14 (HGNC:14001): (PR/SET domain 14) This gene encodes a member of the PRDI-BF1 and RIZ homology domain containing (PRDM) family of transcriptional regulators. The encoded protein may possess histone methyltransferase activity and plays a critical role in cell pluripotency by suppressing the expression of differentiation marker genes. Expression of this gene may play a role in breast cancer. [provided by RefSeq, Dec 2011]

PRDM14 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP7

Synonymous conserved (PhyloP=-0.519 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM14	NM_024504.4 link	c.1629T>C	p.Asp543Asp	synonymous_variant	Exon 8 of 8	ENST00000276594.3	NP_078780.1	Q9GZV8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM14	ENST00000276594.3 link	c.1629T>C	p.Asp543Asp	synonymous_variant	Exon 8 of 8	1	NM_024504.4	ENSP00000276594.2		Q9GZV8

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94830

AN:

151976

Hom.:

29590

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.692

Gnomad AMR

AF:

0.590

Gnomad ASJ

AF:

0.733

Gnomad EAS

AF:

0.735

Gnomad SAS

AF:

0.667

Gnomad FIN

AF:

0.601

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.623

Gnomad OTH

AF:

0.625

GnomAD2 exomes

AF:

0.627

AC:

157495

AN:

251086

AF XY:

0.628

show subpopulations

Gnomad AFR exome

AF:

0.609

Gnomad AMR exome

AF:

0.570

Gnomad ASJ exome

AF:

0.716

Gnomad EAS exome

AF:

0.736

Gnomad FIN exome

AF:

0.601

Gnomad NFE exome

AF:

0.621

Gnomad OTH exome

AF:

0.617

GnomAD4 exome

AF:

0.627

AC:

914929

AN:

1460344

Hom.:

287707

Cov.:

AF XY:

0.627

AC XY:

455750

AN XY:

726444

show subpopulations

African (AFR)

AF:

0.611

AC:

20450

AN:

33450

American (AMR)

AF:

0.570

AC:

25434

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.726

AC:

18942

AN:

26108

East Asian (EAS)

AF:

0.746

AC:

29592

AN:

39690

South Asian (SAS)

AF:

0.647

AC:

55739

AN:

86148

European-Finnish (FIN)

AF:

0.608

AC:

32470

AN:

53400

Middle Eastern (MID)

AF:

0.619

AC:

3313

AN:

5348

European-Non Finnish (NFE)

AF:

0.622

AC:

690741

AN:

1111268

Other (OTH)

AF:

0.634

AC:

38248

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

16995

33989

50984

67978

84973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.624

AC:

94922

AN:

152094

Hom.:

29629

Cov.:

AF XY:

0.622

AC XY:

46231

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.614

AC:

25470

AN:

41474

American (AMR)

AF:

0.590

AC:

9009

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.733

AC:

2546

AN:

3472

East Asian (EAS)

AF:

0.736

AC:

3794

AN:

5158

South Asian (SAS)

AF:

0.669

AC:

3223

AN:

4818

European-Finnish (FIN)

AF:

0.601

AC:

6368

AN:

10588

Middle Eastern (MID)

AF:

0.643

AC:

189

AN:

294

European-Non Finnish (NFE)

AF:

0.623

AC:

42371

AN:

67996

Other (OTH)

AF:

0.626

AC:

1321

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1912

3825

5737

7650

9562

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.627

Hom.:

82910

Bravo

AF:

0.619

Asia WGS

AF:

0.720

AC:

2499

AN:

3478

EpiCase

AF:

0.630

EpiControl

AF:

0.621

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.27

(source)

DANN

Benign

0.35

PhyloP100

-0.52

Mutation Taster

=100/0

polymorphism (auto)

(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

Publications

Loading publications...

8-70052164-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over