8-70052164-A-G

Position:

• chr8-70052164-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_024504.4(PRDM14):​c.1629T>C​(p.Asp543=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PRDM14	NM_024504.4	c.1629T>C	p.Asp543=	synonymous_variant	8/8	ENST00000276594.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM14	ENST00000276594.3	c.1629T>C	p.Asp543=	synonymous_variant	8/8	1	NM_024504.4	P1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94830 AN: 151976 Hom.: 29590 Cov.: 33

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

GnomAD3 exomes AF: 0.627 AC: 157495 AN: 251086 Hom.: 49983 AF XY: 0.628 AC XY: 85247 AN XY: 135682

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 SAS exome AF: 0.651

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.: 43 AF XY: 0.627 AC XY: 455750 AN XY: 726444

Gnomad4 AFR exome AF: 0.611

Gnomad4 AMR exome AF: 0.570

Gnomad4 ASJ exome AF: 0.726

Gnomad4 EAS exome AF: 0.746

Gnomad4 SAS exome AF: 0.647

Gnomad4 FIN exome AF: 0.608

Gnomad4 NFE exome AF: 0.622

Gnomad4 OTH exome AF: 0.634

GnomAD4 genome AF: 0.624 AC: 94922 AN: 152094 Hom.: 29629 Cov.: 33 AF XY: 0.622 AC XY: 46231 AN XY: 74352

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.626

Alfa AF: 0.629 Hom.: 57392

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
DANN	Benign	0.35

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

Other links and lift over

dbSNP: rs10089937; hg19: chr8-70964399; COSMIC: COSV52572526;